Research Of LncRNA SOX21-AS1 In Sponging MiR-31-5p To Promote The Proliferation Of Pancreatic Cancer By Targeting MMP-16

Pancreatic ductal adenocarcinoma(PDAC)is a common tumor of the digestive system and a frequent cause of cancer-related death.Long non-coding RNAs(lncRNAs)have been demonstrated as regulators and tissue-specific biomarkers of multiple cancers,including PDAC.Recent evidence has indicated that the novel lncRNA SOX21-AS1 plays an important role in the progression and metastasis of cancer.However,its function and molecular mechanism in PDAC remain largely unknown.Methods: The expression levels of lncRNA SOX21-AS1 in 20 pairs of pancreatic and paraneoplastic cancer tissues,pancreatic cancer cell lines(Panc1,CAPAN2,CFPAC-1,BXPC3,SW1990)and pancreatic ductal epithelial cells(HPDE)were measured by real-time fluorescence quantitative PCR.Small interfering RNA of lncRNA SOX21-AS1 was transfected into SW1990 and BXPC3 cells by RNA interference technique.The lncRNA SOX21-AS1 low expression cell lines were established and a negative group was set up.MTT and clone formation assays were performed to detect changes in the proliferation ability of SW1990 and BXPC3 cells after knockdown of lncRNA SOX21-AS1.Nucleoplasmic separation PCR assay detected the localization of lncRNA SOX21-AS1 in SW1990 and BXPC3 cells.DIANA database predicted the existence of target binding sequence between lncRNA SOX21-AS1 and miR-31-5p,and dual luciferase reporter gene assay verified the target-regulated relationship.Rescue assays confirmed the regulatory relationship between lncRNA SOX21-AS1 and miR-31-5p.The DIANA database predicted that miR-31-5p had a target binding sequence to the matrix metalloproteinase 16(MMP16)gene,and dual luciferase reporter gene assays verified the targeted regulatory relationship between miR-31-5p and MMP16.The RNA expression of MMP16 was measured in 20 pairs of pancreatic cancer tissues and paraneoplastic tissues using realtime fluorescence quantitative PCR.Results: The expression level of lncRNA SOX21-AS1 was higher in pancreatic cancer tissues than in paraneoplastic tissues.LncRNA SOX21-AS1 expression level was higher in pancreatic cancer cell lines than in HPDE cells,with the highest lncRNA SOX21-AS1 expression level in SW1990 and BXPC3 cells.GEPIA database confirmed that high lncRNA SOX21-AS1 expression is associated with poor prognosis in PDAC.Compared with controls,knockdown of lncRNA SOX21-AS1 significantly inhibited the proliferation of SW1990 and BXPC3 cells.Nucleoplasmic separation PCR experiments revealed that lncRNA SOX21-AS1 was mainly localized in the cytoplasm,and the DIANA database revealed that lncRNA SOX21-AS1 had a target binding sequence to miR-31-5p,and dual luciferase reporter gene experiments confirmed that lncRNA SOX21-AS1 targeted to regulate miR-31-5p.The rescue assay further confirmed that lncRNA SOX21-AS1 competitively bound miR-31-5p.miR-31-5p was predicted to bind to MMP16 in the DIANA database,and the dual luciferase reporter gene assay confirmed that miR-31-5p targeted and regulated MMP16.MMP16 was expressed at higher levels in pancreatic cancer tissues than in paraneoplastic tissues,and miR-31-5p was negatively correlated with MMP16 expression.Conclusions: The expression level of lncRNA SOX21-AS1 was higher in pancreatic cancer tissues than in paraneoplastic tissues.The knockdown of lncRNA SOX21-AS1 inhibited the proliferation of pancreatic cancer SW1990 and BXPC3 cells,and the molecular mechanism may be related to the targeted regulation of miR-31-5p and inhibition of MMP16 expression.