AIM:To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index(BMI) in sporadic colorectal cancer in southern Chinese.METHODS:A hospital-based case-control study was conducted ...AIM:To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index(BMI) in sporadic colorectal cancer in southern Chinese.METHODS:A hospital-based case-control study was conducted from July 2002 to December 2008.There were 706 cases and 723 controls with their sex and age(within 5 years) matched.An unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer.RESULTS:No positive association was observed between smoking status and sporadic colorectal cancer risk.Compared with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer(CRC)(adjusted OR = 8.61 and 95% CI = 6.15-12.05;adjusted OR = 2.30, 95% CI = 1.27-4.17).Moreover, the increased risk of developing sporadic CRC was significant in those with a positive family history of cancer(adjusted OR = 1.62, 95% CI = 1.12-3.34) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.39, 95% CI = 1.10-1.75).Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers(adjusted OR = 7.60 and 95% CI = 5.13-11.25;adjusted OR = 7.52 and 95% CI = 5.13-11.01) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.38 and 95% CI = 1.04-1.83;adjusted OR = 1.35 and 95% CI = 1.02-1.79).The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer(adjusted OR = 2.51 and 95% CI = 1.24-5.07;adjusted OR = 1.82 and 95% CI = 1.17-2.82).CONCLUSION:Alcohol drinking, high BMI(≥ 24.0 kg/m2) and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.展开更多
Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and ...Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared with that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases (P<0.01) and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in p16 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.展开更多
To screen the over differentially expressed genes in carcinoma induced by BPDE-transformed 16HBE cells (16HBE-C cells). Methods The suppression subtractive hybridization (SSH) method was performed to profile diffe...To screen the over differentially expressed genes in carcinoma induced by BPDE-transformed 16HBE cells (16HBE-C cells). Methods The suppression subtractive hybridization (SSH) method was performed to profile differentially expressed genes between 16HBE-C cells and 16HBE cells. The cDNA fragments of differentially expressed genes were inserted into TA cloning vector and transformed competent E. coli strain. Positive clones were randomly picked up and identified by the colony PCR method. Dot blot was used to test the same source with the tester. The differentially expressed cDNA fragments were sequenced and compared with known genes and EST database in Genbank. Results Eight known genes were over-expressed in 16HBE-C cells including eukaryotic translation elongation factor 1 alpha 1, HIF-1 responsive RTP801, ribosomal protein L10 (RPL10), ribosomal protein S29 (RPS29), mitochondrion related genes, and laminin receptor 1. Three differentially expressed cDNA fragments could not be matched to the known genes but to the EST database. Conclusion The SSH method can detect differentially expressed genes between 16HBE-C and 16HBE cells. BPDE-induced carcinogenesis may be related to alteration of at least eight known genes and three unknown genes. These expression data provide a clue to further cloning novel genes and studying functions in BPDE-induced carcinoma.展开更多
Objective To study the alteration of circulating microRNAs in 4-(methylnitrosamino)-l-(3-pyridyl) -l-butanone (NNK)-induced early stage lung carcinogenesis. Methods A lung cancer model of male F344 rats was indu...Objective To study the alteration of circulating microRNAs in 4-(methylnitrosamino)-l-(3-pyridyl) -l-butanone (NNK)-induced early stage lung carcinogenesis. Methods A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 2, 5, 20, and 20 following NNK treatment. Results No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment. Conclusion The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.展开更多
Objective To study the alternative expression and sequence of human elongation factor-1δ (human EF-1δ p31) during malignant transformation of human bronchial epithelial cells induced by cadmium chloride (CdCl2) ...Objective To study the alternative expression and sequence of human elongation factor-1δ (human EF-1δ p31) during malignant transformation of human bronchial epithelial cells induced by cadmium chloride (CdCl2) and its possible mechanism. Methods Total RNA was isolated at different stages of transformed human bronchial epithelial cells (16HBE) induced by CdCl2 at a concentration of 5.0 μM. Special primers and probe for human EF-1δ p31 were designed and expression of human EF-18 mRNA from different cell lines was detected with fluorescent quantitative PCR technique. EF-18 cDNA from different cell lines was purified and cloned into pMD 18-T vector followed by confirming and sequencing analysis. Results The expressions of human EF-1δ p31 at different stages of 16HBE cells transformed by CdCl2 was elevated (P〈0.01 or P〈0.05). Compared with their corresponding non-transformed ceils, the overexpression level of EF-15 p31 was averagely increased 2.9 folds in Cd-pretransformed cells, 4.3 folds in Cd-transformed ceils and 7.2 folds in Cd-tumorigenic cells. No change was found in the sequence of overexpressed EF-1δ p31 at different stages of 16HBE cells transformed by CdCl2. Conclusion Overexpression of human EF-1δ p31 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2, but is not correlated with DNA mutations.展开更多
Chlorophyllin,the sodium and copper salt of chlo-rophyll,has been shown by several investigators tobe an antimutagenic agent.In a previous study wefound that it is a potent inhibitor of the mutagenicactivity of dietar...Chlorophyllin,the sodium and copper salt of chlo-rophyll,has been shown by several investigators tobe an antimutagenic agent.In a previous study wefound that it is a potent inhibitor of the mutagenicactivity of dietary and environmental complex mixtu-res.No information is available,however。展开更多
The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warra...The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warranted.The survival-related pseudogenes retrieved from the Cancer Genome Atlas database were screened by univariate Cox regression analysis and further assessed by least absolute shrinkage and selection operator(LASSO)method.A risk score model based on the prognostic pseudogenes was also constructed.The pseudogene-mRNA regulatory networks were established using correlation analysis,and their potent roles in the ovarian cancer progression were uncovered by functional enrichment analysis.Lastly,ssGSEA and ESTIMATE algorithms was used to evaluate the levels of immune cell infiltrations in cancer tissues and explore their relationship with risk signature.A prediction model of 10-pseudogenes including RPL10P6,AC026688.1,FAR2P4,AL391840.2,AC068647.2,FAM35BP,GBP1P1,ARL4AP5,RPS3AP2,and AMD1P1 was established.The 10-pseudogenes signature was demonstrated to be an independent prognostic factor in patient with ovarian cancer in the random set(hazard ratio[HR]=2.512,95%confidence interval[CI]=2.03–3.11,P<0.001)and total set(HR=1.71,95%CI=1.472–1.988,P<0.001).When models integrating with age,grade,stage,and risk signature,the Area Under Curve(AUC)of the 1-year,3-year,5-year and 10-year Receiver Operating Characteristic curve in the random set and total set were 0.854,0.824,0.855,0.805 and 0.679,0.697,0.739,0.790,respectively.The results of functional enrichment analysis indicated that the underlying mechanisms by which these pseudogenes influence cancer prognosis may involve the immune-related biological processes and signaling pathways.Correlation analysis showed that risk signature was significantly correlated with immune cell infiltration and immune score.We identified a novel 10-pseudogenes signature to predict the survival of patients with ovarian cancer,and that may serve as novel possible prognostic biomarkers and therapeutic targets for ovarian cancer.展开更多
Essential meiotic endonuclease 1 homolog 1 (EME1) is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomi...Essential meiotic endonuclease 1 homolog 1 (EME1) is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME! (i.e.,Ile350Thr: rs12450550T 〉 C and Glu69Asp: rs3760413T 〉 G) and breast cancer risk. We found that compared to the common lie/lie genotype, the Thr variant genotypes (Thr/lle + Thr/Thr) conferred a 1.47-fold increased risk of breast cancer (OR=1.47, 95% CI=I. 13-1.92). The variant Ile350Thr was also associated with early onset of breast cancer (r = -0.116, P = 0.002). The mean age of onset was 44.4 years for Thr/Thr genotype carders and 46.5 years for Thr/lle genotype carriers, which was significantly lower than that (49.4 years) for Ile/Ile genotype carriers (P = 0.006). Moreover, no significant as- sociation was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.展开更多
Objective: To achieve the co-expression of GrB and PFP in Hep-2 cells and analyze the growth inhibiting effects on Hep-2 cells. Methods: Lymphocytes were separated from human laryngeal carcinoma tissue, complete Exo...Objective: To achieve the co-expression of GrB and PFP in Hep-2 cells and analyze the growth inhibiting effects on Hep-2 cells. Methods: Lymphocytes were separated from human laryngeal carcinoma tissue, complete Exon fragments of GrB and PFP were amplified by RT-PCR via extracting lymphocytes total RNA, and they were recombined to the downstream of T7 promoter in the vector pVAX1. The recombinant plasmid pVAX1-PIG was transfected into Hep-2 cells with Lipofectamine 2000. The expression of proteins was identified by RT-PCR, MTT and western blot assay. Results: The gene sequence of the RT-PCR products of GrB and PFP were consistent with the data of GenBank by DNA sequencing analysis. The GrB and PFP cDNA fragment were cloned into the vector of pVAX1 in the right direction and the open reading fragment of GrB and PFP were maintained. The target proteins were detected in the transfected Hep-2 cells, and the inhibitive effect of PFP and GrB on Hep-2 cells growth were studied by thiazolyl blue (MTT) test. Conclusion: The pVAX1-PFP-IRES-GrB plasmid was successfully constructed and expressed, and the expression of PFP and GrB could inhibit the growth of Hep-2 cells.展开更多
Objective: MGMT protein expression has been associated with tumor resistance to alkylating agents. The objective of this paper is to construct the RNA interference vector which can specifically induce the expression ...Objective: MGMT protein expression has been associated with tumor resistance to alkylating agents. The objective of this paper is to construct the RNA interference vector which can specifically induce the expression silence of human DNA repair gene hMGMT. Methods: The hMGMT specific siRNA expression cassette was made by two steps PCR, linked with pUCI 9 to get pU6-MGMTi, co-transfected with pEGFP-CI into 16HBE and screened by G418. The MGMT mRNA and protein levels were detected by RT-PCR and Western Blot respectively. Results: hMGMT specific RNA interfere vector pU6-MGMTi was constructed successfully. In transfected 16HBE cells MGMT mRNA level could hardly be detected and the protein level was only 10% of control. Conclusion: MGMT specific RNAi expression cassette can effectively inhibit MGMT expression. MGMT silence cell line was built by co-transfection technology, which offered condition for studying the gene function of MGMT.展开更多
Radiotherapy is one of the most common countermeasures for treating a wide range of tumors.However,the radioresistance of cancer cells is still a major limitation for radiotherapy applications.Efforts are continuously...Radiotherapy is one of the most common countermeasures for treating a wide range of tumors.However,the radioresistance of cancer cells is still a major limitation for radiotherapy applications.Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy.DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses(DDRs),including those helping cells recover from radiation injuries,such as the activation of DNA damage sensing and early transduction pathways,cell cycle arrest,and DNA repair.Obviously,these protective DDRs confer tumor radioresistance.Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance,and some important advances and breakthroughs have already been achieved in recent years.On the basis of comprehensively reviewing the DDR signal pathways,we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization.We further discuss recent advances identified from preclinical studies,current clinical trials,and clinical application of chemical inhibitors targeting key DDR proteins,including DNA-PKcs(DNA-dependent protein kinase,catalytic subunit),ATM/ATR(ataxia–telangiectasia mutated and Rad3-related),the MRN(MRE11-RAD50-NBS1)complex,the PARP(poly[ADP-ribose]polymerase)family,MDC1,Wee1,LIG4(ligase IV),CDK1,BRCA1(BRCA1 C terminal),CHK1,and HIF-1(hypoxia-inducible factor-1).Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.展开更多
Epithelial-mesenchymal transition(EMT)is a critical cellular process in embryonic development and is also the basis for wound repair,tissue regeneration,and cancer metastasis(Zhao et al.,2015).During cancer migration ...Epithelial-mesenchymal transition(EMT)is a critical cellular process in embryonic development and is also the basis for wound repair,tissue regeneration,and cancer metastasis(Zhao et al.,2015).During cancer migration and invasion,EMT involved comprehensive reprogramming processes related to cytoskeletal remodeling,cell differentiation,epigenetic regulation and metabolism(Plikus et al.,2015).In fact,the understanding of EMT in cancer development is still limited.In 2015.展开更多
Cancer metastasis is the end product of cancer evolution,contributing to the massive mortality of cancer patients(Chaffer and Weinberg,2011).Different primary cancers have distinct spreading routes via the blood or ...Cancer metastasis is the end product of cancer evolution,contributing to the massive mortality of cancer patients(Chaffer and Weinberg,2011).Different primary cancers have distinct spreading routes via the blood or the lymphatics or through both routes,which presents challenge for effective cancer treatment(Qian et aL,2017).展开更多
Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide(anti-BPDE)is a metabolite of benzo[a]pyrene(B[a]P)and acts as a potent mutagen in mammalian systems.However,molecular mechanisms related to anti-BPDE-induced carcinogenesis ar...Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide(anti-BPDE)is a metabolite of benzo[a]pyrene(B[a]P)and acts as a potent mutagen in mammalian systems.However,molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood.Here,we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells(16HBE-T)transformed by exposure to anti-BPDE.The levels of mRNA and pro-tein of c-Myc were examined in the 16HBE-T and vehicle-treated control cells(16HBE-N)by using different meth-ods respectively,including reverse transcriptase-polymer-ase chain reaction(RT-PCR),quantitative real-time PCR(Q-PCR),western blot and immunocytochemical meth-ods.The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T,as compared with those of the 16HBE-N.Likewise,the expression of c-Myc protein was significantly enhanced as compared with those of the control cells.Moreover,the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T.In conclu-sion,the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells,which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.展开更多
Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of≤2.5μm(PM_(2.5)),and a critical trigger ofmost PM_(2.5) exposure-associated diseases.However,the key molecular events r...Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of≤2.5μm(PM_(2.5)),and a critical trigger ofmost PM_(2.5) exposure-associated diseases.However,the key molecular events regulating the PM_(2.5)-induced airway inflammation are yet to be elucidated.Considering the critical role of circular RNAs(circRNAs)in regulating inflammation,we predicted 11 circRNAs that may be involved in the PM_(2.5)-induced airway inflammation using three previously reportedmiRNAs through the starBasewebsite.A novel circRNA circ_0008553 was identified to be responsible for the PM_(2.5)-activated inflammatory response in human bronchial epithelial cells(16HBE)via inducing oxidative stress.Using a combinatorial model PM_(2.5) library,we found that the synergistic effect of the insoluble core and loaded Zn^(2+)ions at environmentally relevant concentrations was the major contributor to the upregulation of circ_0008553 and subsequent induction of oxidative stress and inflammation in response to PM2.5 exposures.Our findings provided new insight into the intervention of PM_(2.5)-induced adverse outcomes.展开更多
基金Supported by Grants from Guangdong Provincial Scientific Research, No. 06104601the National Natural Science Foundation of China, No. 30872488, 30671813 and 30872178
文摘AIM:To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index(BMI) in sporadic colorectal cancer in southern Chinese.METHODS:A hospital-based case-control study was conducted from July 2002 to December 2008.There were 706 cases and 723 controls with their sex and age(within 5 years) matched.An unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer.RESULTS:No positive association was observed between smoking status and sporadic colorectal cancer risk.Compared with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer(CRC)(adjusted OR = 8.61 and 95% CI = 6.15-12.05;adjusted OR = 2.30, 95% CI = 1.27-4.17).Moreover, the increased risk of developing sporadic CRC was significant in those with a positive family history of cancer(adjusted OR = 1.62, 95% CI = 1.12-3.34) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.39, 95% CI = 1.10-1.75).Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers(adjusted OR = 7.60 and 95% CI = 5.13-11.25;adjusted OR = 7.52 and 95% CI = 5.13-11.01) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.38 and 95% CI = 1.04-1.83;adjusted OR = 1.35 and 95% CI = 1.02-1.79).The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer(adjusted OR = 2.51 and 95% CI = 1.24-5.07;adjusted OR = 1.82 and 95% CI = 1.17-2.82).CONCLUSION:Alcohol drinking, high BMI(≥ 24.0 kg/m2) and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.
基金This work was supported by a grant (No. 39170651 and 30200235) from National Natural Science Foundation of China.
文摘Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared with that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases (P<0.01) and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in p16 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.
基金This work was supported by the grants from the National Natural Science Foundation of China (No. 30271111), the Provincial Natural Science Foundation of Guangdong (No. 020734) and National Key Basic Research and Development Program (2002CB512905).
文摘To screen the over differentially expressed genes in carcinoma induced by BPDE-transformed 16HBE cells (16HBE-C cells). Methods The suppression subtractive hybridization (SSH) method was performed to profile differentially expressed genes between 16HBE-C cells and 16HBE cells. The cDNA fragments of differentially expressed genes were inserted into TA cloning vector and transformed competent E. coli strain. Positive clones were randomly picked up and identified by the colony PCR method. Dot blot was used to test the same source with the tester. The differentially expressed cDNA fragments were sequenced and compared with known genes and EST database in Genbank. Results Eight known genes were over-expressed in 16HBE-C cells including eukaryotic translation elongation factor 1 alpha 1, HIF-1 responsive RTP801, ribosomal protein L10 (RPL10), ribosomal protein S29 (RPS29), mitochondrion related genes, and laminin receptor 1. Three differentially expressed cDNA fragments could not be matched to the known genes but to the EST database. Conclusion The SSH method can detect differentially expressed genes between 16HBE-C and 16HBE cells. BPDE-induced carcinogenesis may be related to alteration of at least eight known genes and three unknown genes. These expression data provide a clue to further cloning novel genes and studying functions in BPDE-induced carcinoma.
基金supported by National Key Basic Research Program of China(2012CB525004 to J.Y.)National Natural Science Foundation of China(30972443 to J.Y.)+6 种基金Research Fund for Doctoral Program of Higher Education of China(20114423110002 to J.Y.)Key Program of Guangdong Natural Science Foundation(9251018201000004 to J.Y.)University Talent Program of Guangdong(2010-79 to J.Y.)University Talent Program of Guangzhou(10A003D to J.Y.)Science and Technology Project of Guangzhou(2010Y1-C441 to J.Y.)Youth Foundation of China State Key Laboratory of Respiratory Disease(201105 to W.J.)Medical Scientific Research Foundation of Guangdong Province(A2011234 to W.J.)
文摘Objective To study the alteration of circulating microRNAs in 4-(methylnitrosamino)-l-(3-pyridyl) -l-butanone (NNK)-induced early stage lung carcinogenesis. Methods A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 2, 5, 20, and 20 following NNK treatment. Results No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment. Conclusion The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.
基金Supported by the National Natural Science Foundation of China (No. 30771781)the Natural Science Foundation of Guangdong Province (No.06022672)
文摘Objective To study the alternative expression and sequence of human elongation factor-1δ (human EF-1δ p31) during malignant transformation of human bronchial epithelial cells induced by cadmium chloride (CdCl2) and its possible mechanism. Methods Total RNA was isolated at different stages of transformed human bronchial epithelial cells (16HBE) induced by CdCl2 at a concentration of 5.0 μM. Special primers and probe for human EF-1δ p31 were designed and expression of human EF-18 mRNA from different cell lines was detected with fluorescent quantitative PCR technique. EF-18 cDNA from different cell lines was purified and cloned into pMD 18-T vector followed by confirming and sequencing analysis. Results The expressions of human EF-1δ p31 at different stages of 16HBE cells transformed by CdCl2 was elevated (P〈0.01 or P〈0.05). Compared with their corresponding non-transformed ceils, the overexpression level of EF-15 p31 was averagely increased 2.9 folds in Cd-pretransformed cells, 4.3 folds in Cd-transformed ceils and 7.2 folds in Cd-tumorigenic cells. No change was found in the sequence of overexpressed EF-1δ p31 at different stages of 16HBE cells transformed by CdCl2. Conclusion Overexpression of human EF-1δ p31 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2, but is not correlated with DNA mutations.
文摘Chlorophyllin,the sodium and copper salt of chlo-rophyll,has been shown by several investigators tobe an antimutagenic agent.In a previous study wefound that it is a potent inhibitor of the mutagenicactivity of dietary and environmental complex mixtu-res.No information is available,however。
基金supported by the National Natural Science Foundation of China Grants 81872127,81602289(FQ)81872694,81673267,81473040(JL)+3 种基金81402753,81672303,81871876(LY)Guangzhou Science Research Program General Project Grant 201707010123(FQ)Guangzhou Municipal Scientific Research Project Grant 1201630073(FQ)Guangdong High School Young Innovative Talents Project Grant 2015KQNCX136(FQ).
文摘The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warranted.The survival-related pseudogenes retrieved from the Cancer Genome Atlas database were screened by univariate Cox regression analysis and further assessed by least absolute shrinkage and selection operator(LASSO)method.A risk score model based on the prognostic pseudogenes was also constructed.The pseudogene-mRNA regulatory networks were established using correlation analysis,and their potent roles in the ovarian cancer progression were uncovered by functional enrichment analysis.Lastly,ssGSEA and ESTIMATE algorithms was used to evaluate the levels of immune cell infiltrations in cancer tissues and explore their relationship with risk signature.A prediction model of 10-pseudogenes including RPL10P6,AC026688.1,FAR2P4,AL391840.2,AC068647.2,FAM35BP,GBP1P1,ARL4AP5,RPS3AP2,and AMD1P1 was established.The 10-pseudogenes signature was demonstrated to be an independent prognostic factor in patient with ovarian cancer in the random set(hazard ratio[HR]=2.512,95%confidence interval[CI]=2.03–3.11,P<0.001)and total set(HR=1.71,95%CI=1.472–1.988,P<0.001).When models integrating with age,grade,stage,and risk signature,the Area Under Curve(AUC)of the 1-year,3-year,5-year and 10-year Receiver Operating Characteristic curve in the random set and total set were 0.854,0.824,0.855,0.805 and 0.679,0.697,0.739,0.790,respectively.The results of functional enrichment analysis indicated that the underlying mechanisms by which these pseudogenes influence cancer prognosis may involve the immune-related biological processes and signaling pathways.Correlation analysis showed that risk signature was significantly correlated with immune cell infiltration and immune score.We identified a novel 10-pseudogenes signature to predict the survival of patients with ovarian cancer,and that may serve as novel possible prognostic biomarkers and therapeutic targets for ovarian cancer.
基金supported by the National Natural Science Foundation of China (grants 30671813,30872178,81072366,and 81273149)Guangdong Provincial High Level Experts Grants (No.2010-79)+1 种基金Changjiang Scholars and Innovative Research Team in University grant (No.IRT0961)Guangdong Natural Science Foundation Team Grant (No.10351012003000000 to Dr.J.Lu)
文摘Essential meiotic endonuclease 1 homolog 1 (EME1) is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME! (i.e.,Ile350Thr: rs12450550T 〉 C and Glu69Asp: rs3760413T 〉 G) and breast cancer risk. We found that compared to the common lie/lie genotype, the Thr variant genotypes (Thr/lle + Thr/Thr) conferred a 1.47-fold increased risk of breast cancer (OR=1.47, 95% CI=I. 13-1.92). The variant Ile350Thr was also associated with early onset of breast cancer (r = -0.116, P = 0.002). The mean age of onset was 44.4 years for Thr/Thr genotype carders and 46.5 years for Thr/lle genotype carriers, which was significantly lower than that (49.4 years) for Ile/Ile genotype carriers (P = 0.006). Moreover, no significant as- sociation was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.
基金the Foundation of Doctoral Subject in Jinan University(51205069)the Natural Science Foundation of Guangdong,China(5300804)
文摘Objective: To achieve the co-expression of GrB and PFP in Hep-2 cells and analyze the growth inhibiting effects on Hep-2 cells. Methods: Lymphocytes were separated from human laryngeal carcinoma tissue, complete Exon fragments of GrB and PFP were amplified by RT-PCR via extracting lymphocytes total RNA, and they were recombined to the downstream of T7 promoter in the vector pVAX1. The recombinant plasmid pVAX1-PIG was transfected into Hep-2 cells with Lipofectamine 2000. The expression of proteins was identified by RT-PCR, MTT and western blot assay. Results: The gene sequence of the RT-PCR products of GrB and PFP were consistent with the data of GenBank by DNA sequencing analysis. The GrB and PFP cDNA fragment were cloned into the vector of pVAX1 in the right direction and the open reading fragment of GrB and PFP were maintained. The target proteins were detected in the transfected Hep-2 cells, and the inhibitive effect of PFP and GrB on Hep-2 cells growth were studied by thiazolyl blue (MTT) test. Conclusion: The pVAX1-PFP-IRES-GrB plasmid was successfully constructed and expressed, and the expression of PFP and GrB could inhibit the growth of Hep-2 cells.
文摘Objective: MGMT protein expression has been associated with tumor resistance to alkylating agents. The objective of this paper is to construct the RNA interference vector which can specifically induce the expression silence of human DNA repair gene hMGMT. Methods: The hMGMT specific siRNA expression cassette was made by two steps PCR, linked with pUCI 9 to get pU6-MGMTi, co-transfected with pEGFP-CI into 16HBE and screened by G418. The MGMT mRNA and protein levels were detected by RT-PCR and Western Blot respectively. Results: hMGMT specific RNA interfere vector pU6-MGMTi was constructed successfully. In transfected 16HBE cells MGMT mRNA level could hardly be detected and the protein level was only 10% of control. Conclusion: MGMT specific RNAi expression cassette can effectively inhibit MGMT expression. MGMT silence cell line was built by co-transfection technology, which offered condition for studying the gene function of MGMT.
基金supported by the National Natural Science Foundation of China(Grant Nos.U1803124,81530085,and 31870847)the Natural Science Foundation of Hunan Province(Grant No.2019JJ40396).
文摘Radiotherapy is one of the most common countermeasures for treating a wide range of tumors.However,the radioresistance of cancer cells is still a major limitation for radiotherapy applications.Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy.DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses(DDRs),including those helping cells recover from radiation injuries,such as the activation of DNA damage sensing and early transduction pathways,cell cycle arrest,and DNA repair.Obviously,these protective DDRs confer tumor radioresistance.Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance,and some important advances and breakthroughs have already been achieved in recent years.On the basis of comprehensively reviewing the DDR signal pathways,we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization.We further discuss recent advances identified from preclinical studies,current clinical trials,and clinical application of chemical inhibitors targeting key DDR proteins,including DNA-PKcs(DNA-dependent protein kinase,catalytic subunit),ATM/ATR(ataxia–telangiectasia mutated and Rad3-related),the MRN(MRE11-RAD50-NBS1)complex,the PARP(poly[ADP-ribose]polymerase)family,MDC1,Wee1,LIG4(ligase IV),CDK1,BRCA1(BRCA1 C terminal),CHK1,and HIF-1(hypoxia-inducible factor-1).Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.
基金supported by the National Natural Science Foundation of China(Nos.31671375,31871339 and 31801120)the National Key Research and Development Program of China(No.2017YFC1201200)the research start-up fellowship of University of the Sunshine Coast to MZ.
文摘Epithelial-mesenchymal transition(EMT)is a critical cellular process in embryonic development and is also the basis for wound repair,tissue regeneration,and cancer metastasis(Zhao et al.,2015).During cancer migration and invasion,EMT involved comprehensive reprogramming processes related to cytoskeletal remodeling,cell differentiation,epigenetic regulation and metabolism(Plikus et al.,2015).In fact,the understanding of EMT in cancer development is still limited.In 2015.
基金supported by the National Natural Science Foundation of China(Nos.31171270 and 31671375)the research start-up fellowship of University of the Sunshine Coast to M.Z
文摘Cancer metastasis is the end product of cancer evolution,contributing to the massive mortality of cancer patients(Chaffer and Weinberg,2011).Different primary cancers have distinct spreading routes via the blood or the lymphatics or through both routes,which presents challenge for effective cancer treatment(Qian et aL,2017).
基金supported by the National Natural Science Foundation of China(Grant Nos.30571546,30771780)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,The Ministry of Education of China(No.2007-24)+1 种基金the Natural Science Foundation of Guangdong Province(No.07117550)the Natural Science Key Program of Higher Education Institutions of Guangdong Province,China(No.06Z021).
文摘Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide(anti-BPDE)is a metabolite of benzo[a]pyrene(B[a]P)and acts as a potent mutagen in mammalian systems.However,molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood.Here,we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells(16HBE-T)transformed by exposure to anti-BPDE.The levels of mRNA and pro-tein of c-Myc were examined in the 16HBE-T and vehicle-treated control cells(16HBE-N)by using different meth-ods respectively,including reverse transcriptase-polymer-ase chain reaction(RT-PCR),quantitative real-time PCR(Q-PCR),western blot and immunocytochemical meth-ods.The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T,as compared with those of the 16HBE-N.Likewise,the expression of c-Myc protein was significantly enhanced as compared with those of the control cells.Moreover,the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T.In conclu-sion,the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells,which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.
基金supported by the National Natural Science Foundation of China (Nos.22036002,21906035 and 91643204)the National Key Research&Development Program of China(No.2016YFA0203103)the introduced innovative R&D team project under the“The Pearl River Talent Recruitment Program”of Guangdong Province (No.2019ZT08L387)
文摘Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of≤2.5μm(PM_(2.5)),and a critical trigger ofmost PM_(2.5) exposure-associated diseases.However,the key molecular events regulating the PM_(2.5)-induced airway inflammation are yet to be elucidated.Considering the critical role of circular RNAs(circRNAs)in regulating inflammation,we predicted 11 circRNAs that may be involved in the PM_(2.5)-induced airway inflammation using three previously reportedmiRNAs through the starBasewebsite.A novel circRNA circ_0008553 was identified to be responsible for the PM_(2.5)-activated inflammatory response in human bronchial epithelial cells(16HBE)via inducing oxidative stress.Using a combinatorial model PM_(2.5) library,we found that the synergistic effect of the insoluble core and loaded Zn^(2+)ions at environmentally relevant concentrations was the major contributor to the upregulation of circ_0008553 and subsequent induction of oxidative stress and inflammation in response to PM2.5 exposures.Our findings provided new insight into the intervention of PM_(2.5)-induced adverse outcomes.