MiR-208a-3p Promotes Tumor Progression In NSCLC Via Suppression Of LncRNA-MEG3 Expression

Background Lung cancer is among the most common causes of cancer-related deaths worldwide.Most of patients with this disease are diagnosed in advanced stages and lose the chance of surgical operation.Long non-coding RNAs(lncRNA)are a heterogeneous group of non-coding transcripts more than 200 nt that are involved in many biological processes.MEG3 is a carcinogenesis suppressing lncRNA which downregulated in numerous tumors,including non-small cell lung cancer(NSCLC),hepatocellular carcinoma,gastric cancer,breast cancer and osteosarcoma.But the underlying molecular mechanisms contribute to this dysregulation expression are not entirely known.MiR-208a is reported as an oncomiR recently which is reduced in varies tumor tissues,including tumors.there are few studies on whether miR-208 can interact with MEG3 and how to regulate and control it.Objective We detected the expression level of miR-208a-3p and MEG3 in the NSCLC tissues and adjacent normal tissues and then discussed preliminarily that whether miR-208a-3p could negatively regulated MEG3 expression and promote tumor proliferation and migration in NSCLC.Methods Using RT-PCR,we detected miR-208a-3p and MEG3 expression level in 51 pairs NSCLC tissues and adjacent normal tissues,evaluated the relationship between MEG3 expression and miR-208a-3p expression level in matched tissues and analyzed the association between MEG3 expression and clinic-pathologic characteristics.Then,we examined the expression level of MEG3 and miR-208a-3p in NSCLC cell lines(H975,H1299 and PC-9)and 16HBE,an immortalized normal human bronchial epithelial cell line.Furtherly,applying loss-of-function and gain-of-function approaches,we investigated the role miR-208a-3p in regulation of MEG3 in associated with P53 protein.Results We observed that miR-208a-3p was up-regulation and MEG3 was downregulation in NSCLC tissues,and MEG3 expression was inversely correlated with miR-208a-3p level in NSCLC tissues.MEG3 expression was negatively related with lymphatic node metastasis,differentiation and TNM stage.miR-208a-3p could negatively regulated MEG3 expression and improving the proliferation and migration abilities,which is associated with down-regulation of P53 protein.Conclusion miR-208a-3p could promote NSCLC progression via negatively regulated MEG3 expression,and this promote progression role is associated with downregulating P53 protein.The discovery of a direct regulatory link between miRNAs and lncRNAs provided a new avenue for investigation of mechanisms underlying tumorigenesis.