IncRNA Promotes The Occurrence And Development Of Gastric Cancer And The Preliminary Study Of Its Function And Mechanism

Gastric carcinogenesis is a multi-stepsprocess which involvesproto-oncogenes and tumor suppressor genes,genetic and epigenetic changes.Resent studies show that long noncoding RNA play important role in cell differentiation,proliferation,migration and invation.Many of them are found to be abnormal in GC and play critical role in GC development.Recently,researches on abnormal lncRNAs in GC are limited and it need to screen more lncRNAs and research their molecular mechanism and related pathways.In the first part of this study,we investigate the expression pattern of HAGLROS in GC and its clinical significance as well as its biological role in tumorprogression,upstream transcription factor and downstream pathway.In the second part,we demonstrate that increased HOXC-AS1 expression in GC tissues and cells may be regulated by SP1 and it promote tumor proliferation and migration.In the third part,we investigated the expression pattern of LINC00355 in gastric cancer as well as its biological role in tumor progressionin and EMT.These data suggest that lncRNA could promote the development of GC and regulate gene expression at both transcription and post-transcription levels and may play basic role for futher research on molecular mechanisims and signal transduction pathway in depth.PartⅠ STAT3-inducedupregulatioon of long noncoding RNA HAGLROS promotes GC cell proliferation and migration by mTOR pathwayAIM:The aim of this tudy is to examine the expression pattern of HAGLROS in GC and its clinical significance as well as its biological role in tumor progression.METHODS:Real-time quantitative PCR was performed to detect the relativeexpression of HAGLROS in GC tissues and cells.Gain or loss of function approaches were used to investigate the biological functions of HAGLROS.The effect of HAGLROS on proliferation and apoptotis was evaluated by MTT,colony formation assays.流式,成瘤 And transwell assays and veininjection of cells was used to study the migration of GC cells.ChIP assays were used to investigate role of STAT3 on regulation of HAGLROS in GC cells.RIP,RNA-seq,Western blot were performed to investigate the underlying targets of HAGLROS in GC cells.Results are shownas means ± S.D.and differences were tested for significance using Student’s t-test(two-tailed).RESULTS:HAGLROS expressionwas significantly upregulated both in GC tissuesand cell lines compared with their correspondingcounterparts,and was associated with invasion depth,higher clinical stageof GC patients.Increased expression of HAGLROS in GC was regulated by SP1.Downregulation of HAGLROS expression significantly suppressed cell proliferation,migration,tumor formation and induced cell apoptosis.RNA-seq and Western blotresults showed that mTOR may be the downstream target of HAGLROS.CONCLUSION:Our study demonstrates that STAT3 induced upregulation of HAGLROSmay regulate Mtor to promote GC development.PartⅡ SP1-induced upregulatioon of long noncoding RNA HOXC-AS1 promotes GC cell proliferation and migrationAIM:The aim of this tudy is to detect the expression pattern of HOXC-AS1 in GC and its biological role in tumor progression.METHODS:Real-time quantitative PCR was performed to detect the relativeexpression of HOXC-AS1 in GC tissues and cells.Gain or loss of function approaches were used to investigate the biological functionsof HOXC-AS1.The effect of HOXC-AS1 on proliferation and migration was evaluated by MTT,colony formation assays and wound-healing assays.And transwell assays and veininjection of cells was used to study the migration of GC cells.ChIP and luciferaseassays were used to investigaterole of SP1 on regulation of HOXC-AS1 in GC cells.RIPwas performed to investigate whether HOXC-AS1 could bind to PRC2.Results are shownas means ± S.D.and differences were tested for significance using Student’s t-test(two-tailed).RESULTS:HOXC-AS1 expressionwas significantly upregulated both in GC tissuesand cell lines compared with their correspondingcounterparts.Increased expression of HOXC-AS1 in GC was regulated by SP1.Downregulation ofHOXC-AS 1 expression significantly suppressed the cell proliferation,migration,tumor formation while upregulation of HOXC-AS1 expression promoted cell proliferation and migration.RIP assays result showed that HOXC-AS1 may bind to PRC2 compand to silent target genes.CONCLUSION:Our study demonstrates that SP1 induced upregulation of HOXC-ASlmay regulate downstream target genes to promote GC development.Part ⅢLINC00355 promotes GC cell proliferation and migration AIM:The aim of this study is to detect the expression pattern of LINC00355 in GC and its biological role in tumor progression.METHODS:Real-time quantitative PCR was performed to detect the relativeexpression of LINC00355 in GC tissues and cells.Gain or loss of function approaches were used to investigate the biological functionsof LINC00355.The effect of LINC00355 on proliferationwas evaluated by MTT,colony formation,subcutaneous tumor experiment and flow cytomey.Transwell migration and wound-healing assayswere used to study the migration of GC cells.RIPwas performed to investigate whether LINC00355 could bind to PRC2.Results are shownas means ± S.D.and differences were tested for significance using Student’s t-test(two-tailed).RESULTS:LINC00355 expressionwas significantly upregulated both in GC tissuesand cell lines compared with their correspondingcounterparts.Downregulation ofLINC00355expression significantly suppressed cell proliferation,migration,tumor formation and blocked cell cycle,while upregulation of LINC00355expression promoted cell proliferation and migration.RIP assays result showed that LINC00355 may bind to PRC2 compand to silent target geneLINC00355may s.CONCLUSION:Our study demonstrates that bind to EZH2 to regulate downstream target genes to promote GC development and LINC00355 could progress EMT.