The Role Of MiRNA-149-3p And MiRNA-149-5p In Lung Cancer

Lung cancer is the most common primary malignant tumor of the lung.There are two main types:small cell lung cancer and non-small cell lung cancer.The incidence of non-small cell lung cancer is high,accounting for about 80%of lung cancer patients.Although the level of surgical treatment is increasing with the advancement of science and technology,the clinical treatment effect of patients with non-small cell lung cancer has only slightly improved due to the recurrence and metastasis characteristics of cancer.Therefore,studying the molecular mechanism of non-small cell lung cancer and its potential therapeutic targets plays a very important role.miRNAs are a class of highly conserved non-coding small RNAs that target the regulation of gene expression by base-pair pairing,thereby participating in various life processes.miRNA-149-3p and miRNA-149-5p are cleaved from the same precursor,and their role in human biological processes is not unique.We found that miRNA-149-3p inhibits Lung cancer thr-ough antagonizing NF-?B signaling pathway and AKT signaling pathway,and miRNA-149-5p further aggravates the development of lung cancer by activating the STAT3 signaling pathwayThe experiments of miRNA-149-3p in lung cancer are divided into two parts:in vivo and in vitro.In vivo experiments showed that IFN-?,MCP-1,COX-2,TNF? and other inflammatory genes were significantly increased in WT-type mice and miRNA-149-3p KO mice by intraperitoneal injection of LPS.The inflammatory gene upregulation of miRNA-149-3p KO mice is more obvious.Transfection of miRNA-149-3p mimic in vitro resulted in overexpression of miRNA-149-3p in cells,and found that overexpression miRNA-149-3p can inhibit the expression of CCL-2,iNOS,IP-10 and TNF?.TNF? treatment induces cellular inflammatory response,overexpression miRNA-149-3p can inhibit the expression of CCL-2,iNOS,IP-10 and TNF?induced by TNF?.The luciferase reporter gene assay showed that overexpression miRNA-149-3p can inhibit the transcriptional activity of NF-?B initiated by p65.Cell proliferation assay showed that overexpression miRNA-149-3p can inhibit the proliferation of lung cancer cells;Cell migration assay showed that overexpression miRNA-149-3p can inhibit the migration of lung cancer cells;Western Blot analysis showed that overexpression miRNA-149-3p can inhibit AKT protein phosphorylation induced by TNF?.The experiments of miRNA-149-5p in lung cancer are divided into two parts:in vivo and in vitro.In vivo experiments were carried out by inoculation of different transfecting lung cancer cells to observe the subcutaneous tumor formation in nude mice.It was found that the miRNA-149-5p group had a faster tumor formation and a faster growth rate.Transfection of miRNA-149-5p mimic in vitro resulted in overexpression of miRNA-149-5p in cells,and found that overexpression miRNA-149-5p can promote the expression of iNOS,IP-10,IL-6,MMP-2,MMP-7,IL-1?,VEGF,CyclinD1,CDK6 and other genes;overexpression miRNA-149-5p can promote the migration of lung cancer cells by cell migration assay;overexpression miRNA-149-5p can inhibit the apoptosis of lung cancer cells by FACS assay;overexpression miRNA-149-5p can promote the phosphorylation of STAT3 protein by Western Blot analysis,After inhibition of STAT3 protein activation by using S3I-201 and IL-6 siRNA,it was found that miRNA-149-5p can still promote STAT3 protein phosphorylation.The above experiments show that miRNA-149-3p inhibits Lung cancer through antagonizing NF-?B signaling pathway and AKT signaling pathway,and miRNA-149-5p further aggravates the development of lung cancer by activating the STAT3 signaling pathway.We need to treat the problem dialectically,comprehensive analysis,and provide new ideas for miRNA-149-3p and miRNA-149-5p to become a new target for future lung cancer treatment.