Long Non-protein Coding RNA 961 Inhibits Non-small Cell Lung Cancer Cells Invasion And Migration

Background: Lung cancer is the most common cause of cancer-related death worldwide,in which non-small cell lung cancer(NSCLC)accounts for about 80-85% of all lung cancer cases.Lung cancer is one of the causes of cancer-related death worldwide,in which non-small cell lung cancer(NSCLC)accounts for about 80-85% of all lung cancer cases.Except for protein-coding genes,long noncoding RNAs(lnc RNAs)also turn to be the crucial molecules in NSCLC-associated research field.Given the importance of lnc RNAs in NSCLC,we explored long intergenic non-protein coding RNA 961(LINC00961),which was significantly decreased inNSCLC tissues.Objective:The aim of this study is to evaluate LINC00961 expression in NSCLC tissues,and the influence of LINC00961 on NSCLC cell invasion and metastasis.And to explore its action mechanism.Materials and Methods:(1)Analyze LINC00961 expression levels in two predominant forms of NSCLC(LUAD and LUSC)and normal tissues RNA sequencing data from TCGA.(2)The 48 NSCLC patients were divided into two groups according to the median ratio of LINC00961 levels in tumor tissues: relative low LINC00961 expression group and relative high LINC00961 expression group.(3)Performe q PCR analysis to detect the expression of LINC00961 in diverse human NSCLC cell lines.pc DNA-LINC00961 vector and empty vector were transfected into A549 and PC9 cells.(4)Performe transwell assays to evaluate the influence of LINC00961 on NSCLC cell invasion and migration.(5)To explore the underlying molecular mechanism by which LINC00961 contributes to the NSCLC cells phenotype,we detected the expression of several potential targets involved in cancer cells invasion and migration.Results:In this study,we identified an long intergenic non-protein coding RNA 961(LINC00961),was significantly downregulated in NSCLC tissues.Decreased LINC00961 in NSCLC was associated with higher clinical stage,lymph node metastasis and patients shorter survival time.Further experiments demonstrated that LSD1 could directly bind to LINC00961 promoter regions and epigenetically repress its transcription in NSCLC cells.Moreover,MTT assays showed that LINC00961 had no influence on NSCLC cell proliferation.Ectopic overexpression of LINC00961 could inhibit NSCLC cell migration,invasion in vitro and metastasis in vivo.Finally,western blot analysis revealed that LINC00961 could function as a tumor suppressor partially via affecting ?-catenin expression.Collectively,decreased LINC00961 might play a critical role in NSCLC progression,and could serve as a new prognostic biomarker candidate in human NSCLC.Conclusions:In the present study wu provide that LINC00961 is downregulated in NSCLC tissues,and Decreased LINC00961 is associated with poor prognosis of NSCLC,and Effect of LINC00961 on NSCLC cell proliferation,invasion and migration,and LSD1 represses LINC00961 expression via H3K4me2 modification.