Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report

BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.

TCGA-based analysis of oncogenic signaling pathways underlying oral squamous cell carcinoma

Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.

Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review

BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.

Identification of APEX2 as an oncogene in liver cancer

BACKGROUND DNA damage is one of the critical contributors to the occurrence and development of some cancers.APEX1 and APEX2 are the most important molecules in the DNA damage,and APEX1 has been identified as a diagnostic and prognostic biomarker in liver hepatocellular carcinoma(LIHC).However,the expression of APEX2 and its functional mechanisms in LIHC are still unclear.AIM To examine the expression of APEX2 and the potential mechanism network in LIHC.METHODS We conducted a pan-cancer analysis of the expression of APEX1 and APEX2 using the interactive TIMER tool.GEO datasets,including GSE14520,GSE22058,and GSE64041,were used to compare the APEX2 expression level in tumor tissues and adjacent non-tumor tissues.Then,we calculated the 5-year survival rate according to the web-based Kaplan-Meier analysis.We included the TCGA liver cancer database in GSEA analysis based on the high and low APEX2 expression,showing the potential mechanisms of APEX2 in LIHC.After that,we conducted Pearson correlation analysis using GEPIA2.Next,we performed quantitative polymerase chain reaction(qPCR)assay to examine the APEX2 levels in normal liver cell line LO2 and several liver cancer cell lines,including HepG2,Huh7,SMMC7721,and HCCLM3.APEX2 in HCCLM3 cells was knocked down using small interfering RNA.The role of APEX2 in cell viability was confirmed using CCK-8.Dualluciferase reporter assay was performed to examine the promoter activity of CCNB1 and MYC.RESULTS APEX1 and APEX2 are both highly expressed in the tumor tissues of BLCA,BRCA,CHOL,COAD,ESCA,HNSC,LIHC,LUAD,LUSC,READ,and STAD.APEX2 overexpression in LIHC was validated using GSE14520,GSE22058,and GSE64041 datasets.The survival analysis showed that LIHC patients with high expression of APEX2 had a lower overall survival rate,even in the AJCC T1 patients.High level of APEX2 could indicate a lower overall survival rate in patients with or without viral hepatitis.The GSEA analysis identified that kinetochore and spindle microtubules are the two main cellular components of APEX2 in GO Ontology.APEX2 was also positively associated with molecular function regulation of chromosome segregation and DNA replication.The results of KEGG analysis indicated that APEX2 expression was positively correlated with cell cycle pathway and pro-oncogenic MYC signaling.Pearson correlation analysis showed that APEX2 had a significant positive correlation with CCNB1 and MYC.APEX2 level was higher in liver cancer cell lines than in normal liver LO2 cells.Small interfering RNA could knock down the APEX2 expression in HCCLM3 cells.Knockdown of APEX2 resulted in a decrease in the viability of HCCLM3 cells as well as the expression and promoter activity of CCNB1 and MYC.CONCLUSION APEX2 is overexpressed in LIHC,and the higher APEX2 level is associated with a worse prognosis in overall survival.APEX2 is closely involved in the biological processes of chromosome segregation and DNA replication.APEX2 expression is positively correlated with the pro-oncogenic pathways.Knockdown of APEX2 could inhibit the cell viability and CCNB1 and MYC pathways,suggesting that APEX2 is an oncogene in LIHC,which could be a potential pharmaceutic target in the anti-tumor therapy.

Oncogenes, Oncogenesis, and Oxygen Radicals

The role that free radicals in general and oxygen radicals in particular play in carcinogenesis has attracted considerable attention in recent years. The oxygen radicals are undesirable but inevitable products of aerobic metabolism in the normal living cell. The cellular antioxidant defense system maintains an appropriate balance between necessary oxidative events and those that are excessive. When this critical balance cannot be maintained because of the overloading of the cellularredox system, oxygen radicals can induce cell damage. They can influence carcinogenesis by inducing DN A damage from direct oxidation or indirectly from DNA-binding products of lipid peroxidation. Oxygen radicals can induce conformational changes in the plasma membrane by lipid peroxidation and protein degradation, thus influencing membrane-associated cellular activities. They are capable of affecting membrane-bound protein kinases, growth factors and their receptors, and, therefore, signal transduction and oncogene activation. Thus, the oxygen radicals can have a major influence on oncogenes and oncogenesis. (C)1990 Academic Press.Inc.

Relationship between the high-risk HPV infection and the expression of oncogenes, anti-oncogenes in cervical dysplasia

Objective:To study the relationship between the infection of high-risk HPV in cervical precancerous lesion and the expression of oncogene, anti-oncogene.Methods:218 cases ofcervical intraepithelial neoplasia patients in our hospital during May 2014–May 2016 were chosed and divided into high-risk HPV group (n=107), low-risk HPV group (n=111) according to cervical tissue HPV test;another 100 cases of patients received cervical biopsy and confirmed as benign lesions were enrolled in the control group. RT-PCR method was used to detect the mRNA expression of proto-oncogene and anti-oncogene in three groups, Western-blot method was used to detect the protein expression of Sox-2 and Wnt/β-catenin signal pathway.Results: mRNA expression of oncogene DEK, Bmi-1, c-fos, K-ras, Prdx4 in high-risk HPV group were higher than low-risk HPV group and control group (P<0.05);mRNA expression of anti-oncogene P27, P16, DAPK, PTEN, eIF4E3 in high-risk HPV group were lower than low-risk HPV group and control group (P<0.05);expression of Sox-2 and Wnt/β-catenin signaling pathway protein Sox-2,β-catenin, wnt-1, wnt-3a in high-risk HPV group were higher than low-risk HPV group and control group (P<0.05).Conclusions:High-risk HPV infection can increase the expression of oncogenes and reduce the expression of anti-oncogenes in cervical dysplasia tissues on Sox-2- and Wnt/β-catenin signaling pathway manners.

EXPRESSION OF ONCOGENE AND ANTI-ONCOGENE IN MALE BREAST CARCINOMA

Expression of oncogene and anti-oncogene products in 12 cases of male breast carcinoma was studied.Positive staining was seen in 6 cases for c-myc,6 cases for EGFR.4 cases for c-erbB-2 cases for N-ras,5 cases for Rb and 3 cases for P53.One case was positive and 4 cases were negative for all above mentioned oncogene and antioncogene products.In addition,Cathepsin D(Cath-D),ER.PR,AR.PCNA and AgNOR were also assayed.In all the cases showed c-erbB-2 or P53 positive were Cath-D positive.The significance of expression of c-erbB-2,c-myc,Cath-D,ER and PR in male breast carcinoma was emphatically discussed.

Significance of hepatitis virus infection in the oncogenicinitiation of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.

Study of differential polymerase chain reaction of C-erbB-2 oncogene amplification in gastric cancer

AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic specimens of 83 cases of gastric cancer and 101 metastatic lymph nodes.RESULTS C-erbB-2 amplification was found in 28.9% (24/ 83) surgical specimens and 20.5% (17/ 83) endoscopic ones of gastric cancer patients. The amplification was significant in both types of specimens of advanced cancer cases (P＜0.05) and surgical specimens with lymph node metastasis (P＜0.01). The incidence of C-erbB-2 amplification in lymph nodes with metastasis was higher than in primary sites (surgical specimens, P＜0.05). The patients with amplification tumors had poorer 5-year survival rates than those with unamplification ones in the early cancers and well to moderately differentiated adenocarcinomas (P＜0.05). The same surgical samples were tested again by Southern blot hybridization to ascertain C-erbB-2 amplification, and the positive rate of C-erbB-2 amplification (15.7%) was lower than that of dPCR (28.9%, P＜0.05).CONCLUSION Examining C-erbB-2 amplification by dPCR is a quick, simple, reliable and independent method, and is helpful in predicting prognosis and metastatic potential of gastric cancer.

Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy

A well-known tumor suppressor, p21, acts parado-xically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinogenesis. The molecular behavior of p21 depends on its subcellular localization. Nuclear p21 may inhibit cell proliferation and be proapoptotic, while cytoplasmic p21 may have oncogenic and anti-apoptotic functions. Because most typical tumor suppressive proteins also have different effects according to subcellular localization, elucidating the regulatory mechanisms underlying nucleo-cytoplasmic transport of these proteins would be significant and may lead to a new strategy for anti-hepatocellular carcinoma(HCC) therapy. Chromosome region maintenance 1(CRM1) is a major nuclear export receptor involved in transport of tumor suppressors from nucleus to cytoplasm. Expression of CRM1 is enhanced in a variety of malignancies and in vitro studies have shown the efficacy of specific inhibition of CRM1 against cancer cell lines. Interestingly, interferon may keep p21 in the nucleus; this is one of the mechanisms of its anti-hepatocarcinogenic function. Here we review the oncogenic property of p21, which depends on its subcellular localization, and discuss the rationale underlying a new strategy for HCC treatment and prevention.

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma

Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.

A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

Dual fluorescence in situ hybridization in detection of HER-2 oncogene amplification in primary hepatocellular carcinoma

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.

Oncogenic role of microRNA-423-5p in hepatocellular carcinoma

BACKGROUND： It has been found that microRNA-423-5p （miR423-Sp） is an oncogenic factor and frequently upregulated in gastric carcinoma. However, the involvement of miR423- 5p in hepatocellular carcinoma （HCC） has been rarely reported. The aim of this study was to assess whether miR423-Sp is aberrantly expressed in HCC tissues, and to characterize its roles in the cancerous biology of HCC.

Oncogenic activity of MCM7 transforming cluster

The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is overexpressed and amplified in a variety of human malignancies.MCM7 genome sequence contains a cluster of miRNA that has been shown to downregulate expression of several tumor suppressors including p21,E2F1,BIM and pTEN.The oncogenic potential of MCM7 and its embedded miRNA has been demonstrated vigorously in in vitro experiments and in animal models,and they appear to cooperate in initiation of cancer.MCM7 protein also serves as a critical target for oncogenic signaling pathways such as androgen receptor signaling,or tumor suppressor pathways such as integrinα7 or retinoblastoma signaling.This review analyzes the transforming activity and signaling of MCM7,oncogenic function of miRNA cluster that is embedded in the MCM7 genome,and the potential of gene therapy that targets MCM7.

Oncogenic driver mutations in non-small cell lung cancer: Past, present and future

Lung cancer,of which non-small lung cancer is the most common subtype,represents the leading cause of cancer related-death worldwide.It is now recognized that a significant proportion of these patients present alterations in certain genes that drive oncogenesis.In recent years,more of these so-called oncogenic drivers have been identified,and a better understanding of their biology has allowed the development new targeted agents.This review aims to provide an update about the current landscape of driver mutation in non-smallcell lung cancer.Alterations in Kirsten rat sarcoma,epidermal growth factor receptor,MET,anaplastic lymphoma kinase,c-ROS oncogene 1,v-raf murine sarcoma viral oncogene homolog B,neurotrophic receptor tyrosine kinase,human epidermal growth factor 2,neuregulin-1 and rearranged during transfection are discussed,as well as agents targeting these alterations.Current standards of treatment as well as promising future strategies are presented.Currently,more than fifteen targeted agents are food and Drug administration-approved for seven oncogenic drivers in non-small-cell lung cancer,highlighting the importance of actively searching for these mutations.Continuous and future efforts made in defining the biology of each of these alterations will help to elucidate their respective resistance mechanisms,and to define the best treatment strategy and therapeutic sequence.

Expression of bcl-2 oncogene in gastric precancerous lesions and its correlation with syndromes in traditional Chinese medicine

AIM: To observe the protein and mRNA expression of bcl-2 oncogene in gastric precancerous lesions (GPL) and to analyze its correlation with syndromes in traditional Chinese medicine (TCM). METHODS: Sixty-seven patients with GPL confirmed by gastroscopy and pathology were studied,including 39 cases of moderate gastric mucosal dysplasia,19 cases of severe gastric mucosa dysplasia, 9 cases of incomplete colon metaplasia. In syndrome differentiation of TCM,17 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by qi stagnation, 21 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by stomach heat, 29 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by blood stasis. Protein and mRNA expression of bcl-2 oncogene were detected by labeled streptavidin biotin (LSAB) immunohist-ochemistry and in situ hybridization respectively. RESULTS: Abnormal expression of protein and mRNA on bcl-2 oncogene was found in GPL,which increased gradually with the course of lesions. In moderate and severe gastric mucosal dysplasia and incomplete colon metaplasia,there was no difference in the expression of bcl-2 oncogene (P>0.05).In different accompanying syndromes, the expression of protein and mRNA on bcl-2 oncogene increased gradually in the following order: deficiency of both qi and yin of the spleen and stomach accompanying qi stagnation→stomach heat→blood stasis. In GPL, compared with accompanying blood stasis, there was an obvious difference in the expression of bcl-2 oncogene between the syndrome of qi and yin deficiency of the spleen and stomach and accompanying stomach heat, so did accompanying qi stagnation (the level of protein: X2=8.45, P<0.05;the level of mRNA: X2=7.35, P<0.05). CONCLUSION: Apoptosis-associated bcl-2 oncogene is abnormally expressed in GPL,which correlates with different accompanying syndromes in TCM.

Oncogene GAEC1 regulates CAPN10 expression which predicts survival in esophageal squamous cell carcinoma

AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was stud-ied by using the RNA interference (RNAi) approach through transfecting the GAEC1 -overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1 -targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1 -targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10 ) and upregulation of trinucleotide repeat containing 6C (TNRC6C ) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ± 16.33 vs 12.62 ± 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma.