Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer

BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.

LncRNA HCG18 promotes prostate cancer progression by regulating the miR-512-3p/HK-2 axis

ObjectiveLong non-coding RNAs(lncRNAs)play an important role in tumor progression.Numerous studies show that lncRNAs are strongly associated with prostate cancer(PCa)progression.The aim of this study was to investigate the pathway through which lncRNA HCG18 regulates PCa progression by bioinformatics analysis and experiments.MethodsWe compared HCG18 expression in PCa versus normal tissue and cells by data and cell lines,followed by comparing the changes in tumor cell proliferation,migration,and invasive ability after knockdown of HCG18.Then we searched for its downstream pathway by database and validated the pathway in vivo and in vitro.ResultsHCG18 was highly expressed in PCa and has the ability to promote tumor proliferation,migration,and invasion;knockdown of HCG18 led to a decrease in the ability of cells to do so,which can be reversed by knockdown of miR-512-3p or overexpression of hexokinase 2.ConclusionOur in vivo and in vitro experiments suggest that HCG18 can play a role in promoting PCa progression by blocking the inhibition of hexokinase 2 by miR-512-3p via sponge adsorption.

Value of long non-coding RNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy

BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.

Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.

Effects of long non-coding RNA Opa-interacting protein 5 antisense RNA 1 on colon cancer cell resistance to oxaliplatin and its regulation of micro RNA-137

BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-137 expression,and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSION Highly expressed in CC,OIP5-AS1 can affect the biological behavior of CC cells,and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.

Basic Study Long non-coding RNA TP73-AS1 promotes pancreatic cancer growth and metastasis through miRNA-128-3p/GOLM1 axis

BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic cancer(PC)remain unclear.AIM To investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODS The expression of lncRNA TP73-AS1,miR-128-3p,and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction.The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p.The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation,migration,and invasion abilities were verified by Cell Counting Kit-8,wound-healing,and transwell assays,as well as flow cytometry and Western blot analysis.The interactions among TP73-AS1,miR-128-3p,and GOLM1 were explored by bioinformatics prediction,luciferase assay,and Western blot.RESULTS The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells.High TP73-AS1 expression was correlated with a poor prognosis.TP73-AS1 silencing inhibited PC cell proliferation,migration,and invasion in vitro as well as suppressed tumor growth in vivo.Mechanistically,TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p.CONCLUSION Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis,which might provide a potential treatment strategy for patients with PC.

A novel long non-coding RNA NFIA-AS1 is down-regulated in gastric cancer and inhibits proliferation of gastric cancer cells

Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China.As an important participant in tumor biology,the abnormal expression of long non-coding RNA(lncRNAs)in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor genes.In this study,we identified a novel lncRNA NFIA antisense RNA 1(NFIA-AS1)and explored its role and clinical significance in gastric cancer.Real-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer samples.The lower expression of NFIA-AS1 was significantly associated with larger tumor size,lower histological grade,and advanced TNM stage.Kaplan-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall survival.We also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 levels.In conclusion,our results suggest that the lncRNA NFIA-AS1 may play the role of tumor suppressor gene,and serve as a biomarker for prognosis or progression of gastric cancer.

Silencing of long non-coding RNA CCHE1 inhibits the ovarian cancer SKOV3 cell invasion and migration and inactivates the p38-MAPK signaling pathway

Ovarian cancer(OC)is a major cause of cancer-related deaths among gynaecologicalmalignancies.Emerging studies suggest that the long non-coding RNA(lncRNA)may be the potential biomarker for the diagnosis and prognosis of the cancer.The current study was carried out to investigate the role of lncRNA CCHE1 silencing in OC cell invasion and migration.Expression of lncRNA CCHE1 in normal ovarian cell Hose and OC cell lines HO 8910,A2780 and SKOV3 was detected.LncRNA were transfected with siRNA,and then the proliferation of cells was detected by using MTT assay.Cell invasion and migration was measured by using Transwell assay and scratch test,respectively.The protein levels of E-cadherin,N-cadherin,ERK,p38-MAPK and the phosphorylation of ERK and p38-MAPK in cells after siRNA transfection were detected by using Western blot analysis.Consequently,lncRNA CCHE1 expression was highly expressed in OC cell lines,especially in SKOV3 cells.siRNA1,siRNA2 and siRNA3 all decreased.lncRNA CCHE1 expression in SKOV3 cells and siRNA2 showed the best silencing efficacy.Silencing of lncRNA CCHE1 decreased proliferation,invasion and migration,and reduced the protein levels of N-cadherin,ERK,p38-MAPK and the phosphorylation of ERK and p38-MAPK,while reducing the protein level of E-cadherin in SKOV3 cells.Collectively,our study proved that the silencing of lncRNA CCHE1 could inhibit SKOV3 cell invasion and migration via inactivating the p38-MAPK signaling pathway.

Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma

BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.

LncRNA AFAP1-AS1 exhibits oncogenic characteristics and promotes gemcitabine-resistance of cervical cancer cells through miR-7-5p/EGFR axis

Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy.In our study,the role of long non-coding RNA(lncRNA)AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.Methods:Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method.The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis.The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay.Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium(MTT),soft agar,and colony formation experiments.Cell cycle and apoptosis were detected byflow cytometry.Results:Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis.Besides,patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group.AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells.In addition,AFAP1-AS1 mediated epidermal growth factor receptor(EGFR)expression by serving as a molecular sponge for microRNA-7a-5p(miR-7-5p).This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.Conclusions:In general,the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer,providing potential targets for the management of cervical cancer.

Expressions of Long Non-Coding RNAs in Carcinogenesis of Cervix: A Review

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” with no biological functions. There are many studies conducted on lncRNAs showing they are actively involved in regulation of epigenetic, transcriptional, and post-transcriptional events. Expressions of lncRNAs are more different in many malignant tumors than in benign tumors and normal tissue. Aberration of lncRNAs is responsible to promote or suppress tumorigenesis and cancer progression. Under different circumstances, lncRNAs exhibit their roles in carcinogenesis such as MALAT1 is responsible for intervening mRNA instability, HOTAIR, MALAT1, ANRIL, PVT1 links with miRNA and histonemodifying complexes, MEG3 associates with miRNA, CCAT2, MEG3, GAS5, UCA1 allies with c-Myc or P53 causing suppression of tumor or oncogenesis. Abnormal expressions of lncRNAs are noticed in gynecological cancers, such as cervical cancer, ovarian cancer, and endometrial cancer. Identification of cervical cancer associated lncRNAs is necessary to understand the molecular biogenesis of cancers. In this review, we summarized the foundation and function of the lncRNAs in terms of tumor progression, invasion, prognosis, apoptosis, metastasis, and chemo-resistance. This review will provide references to determine the clinical applications of lncRNAs as ideal diagnostic biomarkers or therapeutic targets in cervical cancers.

前列腺癌组织LncRNA NEAT1、miR-377表达与患者5年生存情况的关系

目的探究前列腺癌组织长链非编码RNA核富集转录本1(LncRNA NEAT1)、微小RNA-377(miR-377)表达与患者5年生存的关系。方法选取2016年7月至2018年8月在邯郸市中心医院住院治疗的98例前列腺癌患者,检测前列腺癌组织及癌旁组织中LncRNA NEAT1、miR-377表达;记录患者5年内生存情况。分析前列腺癌组织LncRNA NEAT1、miR-377与临床病理特征、患者5年生存的关系以及二者的相关性,分析影响患者5年内生存的危险因素及LncRNA NEAT1、miR-377对患者5年内生存的预测价值。结果与癌旁组织比较,前列腺癌组织LncRNA NEAT1显著升高、miR-377显著降低(P<0.05);Ⅲ~Ⅳ期、Gleason评分>7分、血清前列腺特异性抗原(PSA)>10μg/L的患者前列腺癌组织LncRNA NEAT1分别高于Ⅰ~Ⅱ期、Gleason评分≤7分、血清PSA≤10μg/L的患者,miR-377分别低于Ⅰ~Ⅱ期、Gleason评分≤7分、血清PSA≤10μg/L的患者(P<0.05);前列腺癌组织LncRNA NEAT1与miR-377表达呈负相关(P<0.05);LncRNA NEAT1高表达、miR-377低表达患者5年累积生存率分别显著低于LncRNA NEAT1低表达、miR-377高表达患者(P<0.05);与生存组比较,死亡组前列腺癌组织LncRNA NEAT1显著升高,miR-377显著降低(P<0.05);前列腺癌组织LncRNA NEAT1高表达、miR-377低表达、TNM分期Ⅲ~Ⅳ期、Gleason评分>7分、血清PSA水平>10μg/L均是影响前列腺癌患者5年内生存的独立危险因素(P<0.05);前列腺癌组织LncRNA NEAT1和miR-377二者联合预测患者5年内生存的曲线下面积高于LncRNA NEAT1、miR-377各自单独预测(P<0.05)。结论前列腺癌组织LncRNA NEAT1呈高表达、miR-377呈低表达,对患者5年内生存具有较高的预测价值。

血清lncRNA PCAT1、miR-128-3p水平与结肠癌患者病理特征及术后肝转移的关系研究

目的探讨血清长链非编码核糖核酸(LncRNA)前列腺癌相关转录因子1(PCAT1)、微小RNA-128-3p(miR-128-3p)水平与结肠癌患者病理特征及术后肝转移的关系。方法选取2019年2月至2021年1月期间邯郸市中心医院收治的接受手术治疗的157例结肠癌患者(结肠癌组)为研究对象,55例同期健康体检者作为对照组。采用实时荧光定量PCR法检测并比较两组血清LncRNA PCAT1、miR-128-3p表达水平,分析结肠癌患者血清LncRNA PCAT1与miR-128-3p表达水平的相关性,分析血清LncRNA PCAT1、miR-128-3p表达水平与结肠癌临床病理特征的关系。随访3年,统计结肠癌术后肝转移发生率,采用单因素和多因素Logistic回归模型分析结肠癌术后肝转移的危险因素,采用受试者工作特征(ROC)曲线分析血清LncRNA PCAT1、miR-128-3p对结肠癌术后肝转移的预测价值。结果与对照组相比,结肠癌组血清LncRNA PCAT1表达水平升高,miR-128-3p表达水平降低(P<0.05);Pearson相关性分析发现结肠癌患者血清LncRNA PCAT1表达水平与血清miR-128-3p呈负相关(r=-0.661,P<0.001)。不同TNM分期患者血清LncRNA PCAT1表达水平比较,Ⅰ期<Ⅱ期<Ⅲ期;血清miR-128-3p表达水平比较,Ⅰ期>Ⅱ期>Ⅲ期(P<0.05)。无淋巴结转移、未侵犯浆膜层相比,有淋巴结转移、侵犯浆膜层的结肠癌患者血清LncRNA PCAT1表达水平均较高,血清miR-128-3p表达水平均较低(P<0.05)。随访3年,结肠癌术后肝转移发生率为25.48%(40/157)。多因素Logistic回归分析显示,TNM分期Ⅲ期、有淋巴结转移、血清LncRNA PCAT1表达水平升高是影响结肠癌术后肝转移的独立危险因素(P<0.05),血清miR-128-3p表达水平升高是保护因素(P<0.05)。ROC曲线分析显示,血清LncRNA PCAT1、miR-128-3p单独及二者联合预测结肠癌术后肝转移的AUC分别为0.761、0.763、0.836,二者联合预测的灵敏度高于单独预测(P<0.05)。结论结肠癌患者血清LncRNA PCAT1高表达、miR-128-3p低表达,两者与TNM分期、淋巴结转移、侵犯浆膜层及术后肝转移密切相关,可作为预测结肠癌术后肝转移的潜在辅助性指标。

LncRNA PVT1 promotes ovarian cancer progression by silencing miR-214

Objective: Emerging evidence indicates that long non-coding RNAs(lnc RNAs) are critical in carcinogenesis and progression of ovarian cancer. This study aimed to explore the functions and molecular mechanisms of plasmacytoma variant translocation I(PVT1) in ovarian cancer Methods: PVT1 and miR-214 were detected by qRT-PCR assays in ovarian cancer tissues and cells. The cell proliferation,migration, and invasion abilities were detected by cell functional experiments, respectively. Western blot assay was performed to detect epithelial-mesenchymal transition(EMT) markers. MiR-214 expression regulated by PVT1 was studied by RNA immunoprecipitation(RIP) and chromatin immunoprecipitation(Ch IP) assays.Results: The expression of PVT1 was up-regulated in ovarian cancer tissues and cell lines. Elevated PVT1 expression was associated with advanced stage and indicated poor prognosis for ovarian cancer patients. The knockdown of PVT1 impaired SKOV3 cell proliferation, migration, and invasion in vitro. The promotion of ovarian cancer progression by PVT1 involved in regulation of the epithelial-mesenchymal transition process and PVT1 interaction with EZH2 represses miR-214 expression in ovarian cancer cells.Conclusions: PVT1 plays an important role in ovarian cancer tumorigenesis, which might be as a novel diagnostic marker and therapeutic target for ovarian cancer.

lncRNA MIF-AS1调节miR-423-5p/PYCR1轴对前列腺癌细胞恶性生物学行为的影响

目的探究长链非编码RNA(lncRNA)巨噬细胞移动抑制因子反义RNA1(MIF-AS1)调节miR-423-5p/吡咯啉-5-羧酸还原酶1(PYCR1)轴对前列腺癌(PC)细胞恶性生物学行为的影响。方法体外培养PC3细胞,敲低MIF-AS1或下调miR-423-5p表达,检测PC患者肿瘤组织与癌旁组织和细胞中MIF-AS1、miR-423-5p和PYCR1 mRNA的表达;检测细胞增殖、凋亡、迁移与侵袭;Western blot检测PYCR1蛋白表达;验证miR-423-5p和MIF-AS1、PYCR1的关系。结果MIF-AS1、PYCR1 mRNA在肿瘤组织中呈高表达,miR-423-5p呈低表达。沉默MIF-AS1可抑制PC3细胞增殖、迁移、侵袭及PYCR1表达,上调miR-423-5p表达,诱导细胞凋亡(P<0.05);抑制miR-423-5p表达可逆转沉默MIF-AS1对PC3细胞恶性行为的抑制作用(P<0.05)。MIF-AS1、PYCR1与miR-423-5p存在靶向调控关系。结论沉默MIF-AS1可能通过上调miR-423-5p来抑制PYCR1表达,抑制PC细胞的恶性行为。

LncRNA TPT1-AS1在前列腺癌中的表达及对生物学功能的影响

目的:研究长链非编码RNA(LncRNA)肿瘤蛋白翻译调节因子1(TPT1)-反义RNA1(AS1)对前列腺癌细胞增殖、侵袭的影响。方法:体外培养人正常前列腺上皮细胞(RWPE-1)和前列腺癌细胞系雄激素非依赖f生前列腺癌(LNCaP)、DU-145、PC-3、22RV1,实时荧光定量PCR(qRT-PCR)检测各细胞系中LncRNA TPT1-AS1表达水平;选取表达差异最大的细胞系PC-3、DU-145,阳离子脂质体LipofectamineTM 2000瞬时转染si-RNATPT1-AS1阴性对照(si-RNA对照)组和siRNA-TPT1-AS1干扰(siRNA-TPT1-AS1干扰)组,不添加任何试剂设为空白对照组。qRT-PCR验证siRNA-TPT1-AS1转染情况;CCK-8检测TPT1-AS1-sh对细胞增殖的影响;Transwell检验TPT1-AS1-sh对细胞侵袭的影响;免疫印记(WB)法检测细胞TPT1蛋白的变化。结果:与正常前列腺细胞系RWPE-1相比,前列腺癌细胞系LNCaP、DU-145、PC-3、22RV1中TPT1-AS1的水平显著升高(P<0.05)。在DU-145、PC-3中,空白对照组与si-RNA对照组中TPT1-AS1表达量、0,6,12,24,36,48 h各时期450 nm处的吸光度(A450)值、侵袭细胞数量、TPT1蛋白表达量差异均无统计学意义(P>0.05);与空白对照组、si-RNA对照组相比,siRNATPT1-AS1干扰组中TPT1-AS1表达量,24,36,48 h细胞A450值、细胞侵袭数量、TPT1蛋白表达量显著降低(P<0.05)。在DU-145中,与空白对照组、si-RNA对照组相比,siRNA-TPT1-AS1干扰组12 h细胞A450值显著降低(P<0.05)。结论:前列腺癌细胞系中TPT1-AS1表达上调;干扰前列腺癌细胞系DU-145、PC-3中TPT1-AS1可抑制细胞增殖、侵袭。

lncRNA TUG1和PCAT-1表达水平与多发性骨髓瘤预后的关系及其诊断价值分析

目的探讨长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)和前列腺癌相关转录产物1(PCAT-1)在多发性骨髓瘤(MM)患者血清中的表达水平及与预后的关系,并探讨其诊断价值。方法选取2013年1月至2016年11月于该院住院治疗的MM患者90例作为MM组,另选取90例健康体检者作为对照组。采用实时荧光定量PCR检测血清lncRNA TUG1和PCAT-1的表达水平;分析lncRNA TUG1和PCAT-1的表达水平与临床病理特征的关系;分析lncRNA TUG1和PCAT-1的表达水平与MM患者预后的关系;采用COX风险回归模型分析影响患者预后的危险因素;使用受试者工作特征(ROC)曲线分析TUG1和PCAT-1对MM的诊断价值。结果MM组患者的血清lncRNA TUG1和PCAT-1表达水平高于对照组(P<0.05);lncRNA TUG1高表达组与低表达组、lncRNA PCAT-1高表达组与低表达组在年龄、β2微球蛋白和Ca2+水平方面比较,差异均有统计学意义(P<0.05);lncRNA TUG1高表达组3年生存率低于lncRNA TUG1低表达组(P<0.05),lncRNA PCAT-1高表达组3年生存率低于lncRNA PCAT-1低表达组(P<0.05)。多因素COX风险回归模型分析显示,年龄较大、β2微球蛋白水平较高、lncRNA TUG1高表达和PCAT-1高表达是影响MM患者预后的危险因素(P<0.05)。血清lncRNA TUG1的曲线下面积为0.777(95%CI:0.704~0.850);血清lncRNA PCAT-1的曲线下面积为0.648(95%CI:0.566~0.729)。结论血清lncRNA TUG1和PCAT-1在MM患者中高表达,lncRNA TUG1辅助诊断MM的价值优于lncRNA PCAT-1,血清lncRNA TUG1和PCAT-1表达水平与MM患者的预后相关。

声门上型喉癌患者血清LncRNA PCAT1、miR-210表达与预后的关系

目的探讨血清长链非编码RNA前列腺癌相关转录因子1(LncRNA PCAT1)、微小RNA-210(miR-210)表达与早期声门上型喉癌术后复发的相关性。方法选取2013年12月~2017年12月于本院就诊的早期声门上型喉癌患者120例为观察组,术后随访24个月,复发患者21例为复发组,未复发患者99例为非复发组,另选择同期于本院进行体检的健康者120例为对照组。采用实时荧光定量PCR(qRT-PCR)法检测血清LncRNA PCAT1、miR-210水平;采用Logistic回归分析影响早期声门上型喉癌患者术后复发的危险因素;采用ROC曲线分析血清LncRNA PCAT1、miR-210对早期声门上型喉癌患者术后复发的预测价值。结果观察组血清LncRNA PCAT1水平显著高于对照组(P<0.05),血清miR-210水平显著低于对照组(P<0.05);复发组血清LncRNA PCAT1水平显著高于非复发组(P<0.05),血清miR-210水平显著低于非复发组(P<0.05)。Logistic回归分析结果显示,T分期为T2期、血清LncRNA PCAT1高表达、miR-210低表达均是影响早期声门上型喉癌患者术后复发的独立危险因素(P<0.05)。ROC曲线分析结果显示,血清LncRNA PCAT1预测早期声门上型喉癌患者术后复发的曲线下面积为0.899,截断值为1.601,敏感度为81.0%,特异性为98.0%。血清miR-210预测早期声门上型喉癌患者术后复发的曲线下面积为0.764,截断值为0.902,敏感度为90.5%,特异性为60.6%。血清LncRNA PCAT1、miR-210联合预测早期声门上型喉癌患者术后复发的曲线下面积为0.925,敏感度为81.0%,特异性为99.0%。结论早期声门上型喉癌患者血清LncRNA PCAT1水平升高,血清miR-210水平降低,均是影响早期声门上型喉癌患者术后复发的独立危险因素,对评估早期声门上型喉癌患者术后复发具有一定价值。

长链非编码RNA PlncRNA-1在前列腺癌中的表达及其意义

目的:探讨长链非编码RNA PlncRNA-1在前列腺癌中的表达及其意义。方法:选取12例前列腺癌患者病理组织为观察组(Pca组),另选取12例良性前列腺增生病理组织为对照组(BPH组),采用qRT-PCR方法检测两组间PlncRNA-1mRNA相对表达水平间差异。同时将雄激素依赖的前列腺癌细胞系LNCa P分为两组,根据是否采用siRNA下调PlncRNA-1表达水平分为PlncRNA-1-siRNA组和Negative control(NC)组。采用qRT-PCR方法检测两组间PlncRNA-1 mRNA相对表达水平。采用Western Blot方法检测两组间细胞周期蛋白Cyclin D1表达水平。采用CCK-8法检测第1、2、3、4、5天两组细胞增殖情况,比较两组细胞间增殖速率间差异。结果:Pca组患者组织标本中PlncRNA-1 mRNA表达水平为(2.48±0.37),较BHP患者组织(1.19±0.28)显著升高(P=0.031)。PlncRNA-1-siRNA组细胞中PlncRNA-1 mRNA相对表达量(1.43±0.69)较NC组细胞株(2.54±0.41)明显降低(P=0.028)。经siRNA下调PlncRNA后,PlncRNA-1-siRNA组细胞中Cyclin D1蛋白水平显著较NC组降低(P<0.05)。PlncRNA-1-siRNA组细胞株增值速率较NC组细胞明显下降(P<0.05)。结论:长链非编码RNA PlncRNA-1的高表达参与了前列腺癌的发病过程,促进细胞周期蛋白Cyclin D1的表达从而促进肿瘤细胞增殖可能是其参与发病的机制之一。

长链非编码RNA MALAT1与前列腺癌的关系

前列腺癌通常是指前列腺腺泡上皮来源的恶性肿瘤,已成为威胁老年男性健康的全球性“杀手”.前列腺癌的进展机制以及治疗策略一直是研究的重点,近年来,长链非编码RNA似乎在这当中发挥重要的作用.长链非编码RNA MALAT1在前列腺癌进展、治疗中发挥关键的作用,其不仅影响前列腺癌生物学特性,在肿瘤转移、侵袭、细胞增殖等方面都起到关键的作用,而且在肿瘤药物治疗中起到调节作用,其作用机制与ceRNA、AR信号通路等有关.本文就长链非编码RNA MALAT1与前列腺癌的关系作一综述,希望能为前列腺癌的诊治提供新的研究方向.