| Recent evidence indicates that long noncoding RNAs(lncRNAs)play a critical role in the regulation of cellular processes,such as differentiation,proliferation and metastasis.These lncRNAs are found to be dysregulated in a variety of cancers.lncRNA BANCR and SPRY4-IT1 are mis-regulated in multiple cancers;however,The clinical significance of BANCR and SPRY4-IT1,and their molecular mechanisms controlling cancer cell migration and metastasis are unclear.Meanwhile,the roles of lncRNA HOXA11-AS in cancer development is unknown.Therefore,the aim of this studies is to investigate the role of BANCR,SPRY4-IT1,and HOXA11-AS in NSCLC and gastric cancer development.In the first part of this study,we investigate the expression pattern of BANCR in NSCLC and its clinical significance as well as its biological role in tumor progression.In the second part,we demonstrate that decreased SPRY4-IT1 expression may be regulated by EZH2.SPRY4-IT1 is a characteristic molecular change in NSCLC and the effect of SPRY4-IT1 on the phenotypes of NSCLC cells was investigated both in vitro and in vivo.We also investigated the expression pattern of HOXA11-AS in gastric cancer as well as its biological role in tumor progression in the third part.Moreover,the mechanism that E2F1 promotes HOXA11-AS transcription and HOXA11-AS regulated underlying target genes was investigated.These data suggest that lncRNA could regulate gene expression at both transcription and post-transcription levels and contribute to cancers development.This study will enhance our knowledge to better understand the pathogenesis and development of NSCLC and gastric caner,and facilitate the development of lncRNA-directed diagnostics and therapeutics against these diseases.Part I Downregulation of BANCR is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transitionAIM: The aim of this study is to examine the expression pattern of BANCR in NSCLC and its clinical significance as well as its biological role in tumor progression.METHODS: Real-time quantitative PCR was performed to detect the relative expression of BANCR in NSCLC tissues and cells.Gain or loss of function approaches were used to investigate the biological functions of BANCR.The effect of BANCR on proliferation was evaluated by MTT,colony formation assays,Tunel staining and transwell assays and vein injection of cells was used to study the invasion and metastasis of NSCLC cells.q RT-PCR,western blot assays and immunofluorescence assays were performed to investigate the underlying targets of BANCR in NSCLC cells.Results are shown as means ± S.D.and differences were tested for significance using Student's t-test(two-tailed).RESULTS: BANCR expression was significantly down-regulated both in NSCLC tissues and cell lines compared with their corresponding counterparts.Decreased expression of BANCR in NSCLC tissues was associated with tumor size,a higher clinical stage,and was also correlated with shorter overall survival of NSCLC patients.Exogenous up-regulation of BANCR expression significantly suppressed the cell proliferation,invasion and metastasis,and induced cell apoptosis.Western blot assays and immunofluorescence results showed that BANCR could affect NSCLC cells EMT process.CONCLUSION: Our study demonstrates that down-regulated BANCR contributes to NSCLC development,and would be targets for NSCLC therapies and further developed as potential prognostic factors.Part?EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transitionAIM: The aim of this study is to examine the expression pattern of SPRY4-IT1 in NSCLC and its clinical significance as well as its biological role in tumor progression.METHODS: Real-time quantitative PCR was performed to detect the relative expression of SPRY4-IT1 in NSCLC tissues and cells.Gain or loss of function approaches were used to investigate the biological functions of SPRY4-IT1.Ch IP assays were used to investigate role of EZH2 on regulation of SPRY4-IT1 in NSCLC cells.The effect of SPRY4-IT1 on proliferation was evaluated by MTT,colony formation assays,Tunel staining assays.And transwell assays and vein injection of cells was used to study the invasion and metastasis of NSCLC cells.QRT-PCR,western blot assays and immunofluorescence assays were performed to investigate the underlying targets of SPRY4-IT1 in NSCLC cells.Results are shown as means ± S.D.and differences were tested for significance using Student's t-test(two-tailed).RESULTS: SPRY4-IT1 expression was significantly down-regulated both in NSCLC tissues and cell lines compared with their corresponding counterparts.Decreased expression of SPRY4-IT1 in NSCLC was regulated by EZH2 and was associated with tumor size,a higher clinical stage,and was also correlated with shorter overall survival of NSCLC patients.Exogenous up-regulation of SPRY4-IT1 expression significantly suppressed the cell proliferation,invasion and metastasis,and induced cell apoptosis.Western blot assays and immunofluorescence results showed that SPRY4-IT1 could affect NSCLC cells EMT process.CONCLUSION: Our study demonstrates that down-regulated SPRY4-IT1 contributes to NSCLC development,and would be targets for NSCLC therapies and further developed as potential prognostic factors.Part ? long non coding RNA HOXA11-AS contributes to gastric cancer cells proliferation and metastasis by regulating PRSS8 and KLF2AIM: The aim of this study is to examine the expression pattern of HOXA11-AS in gastric cancer and its clinical significance as well as its biological role in tumor progression.METHODS: Bioinformatics analysis and real-time quantitative PCR was performed to detect the relative expression of HOXA11-AS in gastric cancer tissues and cells.Gain or loss of function approaches were used to investigate the biological functions of HOXA11-AS.Ch IP and luciferase report assays were used to investigate role of E2F1 on regulation of HOXA11-AS in gastric cancer cells.The effect of HOXA11-AS on proliferation and apoptosis was evaluated by MTT,colony formation assays,Tunel and Edu staining assays.Transwell assays and vein injection of cells was used to study the invasion and metastasis of gastric cancer cells.RIP,RNA-seq,and q PCR assays were performed to investigate the underlying targets of HOXA11-AS in gastric cancer cells.Results are shown as means ± S.D.and differences were tested for significance using Student's t-test(two-tailed).RESULTS: HOXA11-AS expression was significantly up-regulated both in gastric cancer tissues and cell lines compared with their corresponding counterparts.Increased expression of HOXA11-AS in gastric cancer was regulated by E2F1.Exogenous down-regulation of HOXA11-AS expression significantly suppressed the cell proliferation,invasion and metastasis,and induced cell apoptosis.RNA-seq,RIP and q PCR assays results showed that HOXA11-AS may regulate PRSS8 and KLF2 expression by recruiting PRC2/LSD1/DNMT1/STAU1 in gastric cancer cells.CONCLUSION: Our study demonstrates that up-regulated HOXA11-AS contributes to gastric cancer development,and would be targets for gastric cancer therapies and further developed as potential prognostic factors. |
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