The Regulatory Mechanism Research Of MiR-411 In Non-small Cell Lung Cancer

Lung cancer is one of the most common cancers in the world,with the highest mortality in our country.Lung cancer contains non-small cell lung cancer(NSCLC)and small cell lung cancer(SCLC).NSCLC accounts for about 85% among all lung cancer,and the 5-year survival rate is approximately 15%.Micro RNAs(miRNAs)are a class of single stranded small noncoding RNAs,18–25 nucleotides(nt)in length.They regulate gene expression on the post-transcriptional level via binding to the 3?-untranslated region(3?-UTR)of the target m RNA,thereby affect a variety of major diseases development and tumorigenesis.Our data revealed that the expression level of miR-411(-5p/3p)was significantly increased in human NSCLC tissues and cell lines,compared with controls.H1299 and SPCA-1 cells were stably transfected with miR-411(p Lenti-miR-411)or an empty vector(p Lenti).Overexpression of miR-411 significantly promotes NSCLC cells proliferation and migration,and impede cell apoptosis.We predicted the potential target genes with miRWalk 2.0 combined with two sets of lung cancer microarray data(GSE19188 and GSE51852).Dual luciferase reporter assay demonstrated that suppressor gene SPRY4 was a common target of miR-411-5p and miR-411-3p.Knockdown of endogenous SPRY4 achieved the similar effects with overexpression of miR-411 in NSCLC cells.SPRY4 expression vector could rescue the effects of miR-411-overregulation in H1299 cells.At last,SCID mice were injected subcutaneously with p Lenti-miR-411 H1299.The results showed that miR-411 promoted tumor growth and weight.Moreover,q RT-PCR,western blot and immunohistochemistry assays revealed that miR-411 inhibited protein level of SPRY4,increased epidermal growth factor receptor(EGFR)and regulated E-cadherin and N-cadherin expression,involved inepithelial-mesenchymal transition(EMT).Meanwhile we studied another target of miR-411-5p,thioredoxin interacting protein (TXNIP).MiR-411 improved SPCA-1 cell cycle progress through decreasing TXNIP expression,but didn?t in H1299 cells.It could be due to cell-specific of TXNIP.Collectively,miR-411 required for NSCLC development by suppressing SPRY4 and TXNIP,might be promote tumor metastasis by inducing EMT.In conclusion,miR-411 could be potential target for lung cancer therapy in future.