Research On The Mechanism Of Long Non-Coding RNA LINC00922 Promoting The Progression Of Gastric Cancer And Inhibiting Chemosensitivity

Objective:Long non-coding RNA(LncRNA)LINC00922 was first reported as a carcinogenic factor in lung cancer,however,its role and mechanism in gastric cancer(GC)remain unknown.This study first detected the expression level of LINC00922 in GC tissues,and explored the diagnostic and prognostic value of LINC00922 based on clinicopathological data.The effect of LINC00922 on the biological behavior of GC cells was further studied,and the possible mechanism of its regulation on the progression of GC and chemotherapy sensitivity was explored,and its potential therapeutic value was evaluated.Methods:(1)Gastric adenocarcinoma data were downloaded from The Cancer Genome Atlas(TCGA)database.And the target gene LINC00922 was elect out based on the reported literature combined.(2)The expression level of LINC00922 was detected by reverse transcription quantitative polymerase chain reaction(RT-qPCR)in 112 GC and adjacent control tissue samples collected from our center.The correlation between each clinicopathological feature and the expression level of LINC00922 was evaluated respectively.We evaluated the correlation between differential expression of LINC00922 and five-year overall survival rate in patients with GC.The expression level of LINC00922 in plasma samples of patients with GC and healthy subjects was detected.The sensitivity and specificity of LINC00922 in the diagnosis of GC were evaluated by receiver operating curve(ROC).(3)The expression of LINC00922 in GC cell lines was detected by RT-qPCR.Specific si RNA oligonucleotide was designed for LINC00922,and LINC00922 was knocked down by lipofection.Cell proliferation ability was analyzed by cell counting and cloning assay,migration and invasion ability was analyzed by Transwell assay,and apoptosis level was detected by flow cytometry.(4)The changes of downstream genes caused by LINC00922 silencing were investigated and the potential target genes were screened.The subcellular localization of LINC00922 was evaluated by nucleocytoplasmic separation test.(5)The activity and cell death levels of GC cells treated with cisplatin and paclitaxel were evaluated by MTT and flow cytometry,and the effect of LINC00922 silencing on the above processes was further evaluated.(6)Western blot was used to analyze the effect of LINC00922 silencing on the expression of apoptosis-related proteins under the action of chemotherapy drugs.Results:(1)In the TCGA database,LINC00922 was highly expressed in GC tissues.(2)LINC00922 was highly expressed in clinical GC samples.Higher expression level of LINC00922 was correlated with positive lymphnodes metastasis and advanced TNM stage.Patients with high expression of LINC00922 in tumor tissues had worse overall survival.The area under ROC curve of plasma LINC00922 for diagnosis of GC was 0.727(95%CI:0.604～0.849).(3)The expression of LINC00922 was generally up-regulated in all GC cell lines.Knockdown of LINC00922 significantly inhibited the proliferation,migration and invasion of AGS and HGC-27,and induced their apoptosis.(4)Knockdown of LINC00922 led to up-regulation of apoptosis-related protein BAX and downregulation of Bcl-xL.The results of nuclear separation assay showed that LINC00922 was mainly distributed in the cytoplasm.(5)Both cisplatin and paclitaxel could inhibit the viability and induce apoptosis of GC cells in a concentration-dependent manner.Silencing LINC00922 further enhanced the chemosensitivity of GC cells.(6)Cisplatin and paclitaxel could increase the level of BAX and inhibit the level of Bcl-xL in GC cells.The effect was further enhanced by LINC00922 silencing.Conclusion:LncRNA LINC00922 is highly expressed in GC tissues,cells and plasma of patients,and its expression level has potential value in the diagnosis,staging and prognosis evaluation of GC.LINC00922 regulates the progression of GC by promoting proliferation,migration and invasion,and inhibiting apoptosis.In addition,LINC00922 may inhibit the chemotherapy sensitivity of GC cells through BAX and Bcl-xL.