Long non-coding RNA Xist promotes progression of non-small-cell lung cancer (NSCLC) by modulating miR-103a and MAP3K3 pathway

Background: Non-small-cell lung carcinoma (NSCLC) is the most common type of lung cancer with poor prognosis despite advent of newer treatment modalities. The role of long non-coding RNA (lncRNA)-Xist in cancer including NSCLC has already been established. Hence, understanding the underlying mechanism of action of lncRNA-Xist in NSCLC might provide basis for novel drug targets. Objective: In this study, we explored the underlying molecular mechanism through which lncRNA-Xist promotes NSCLC progression. Materials and methods: In the human lung cancer cell line A549, cell proliferation and percentage of apoptotic cells were measured by MTT assay and flow cytometry. Western blot analysis was done to explore the expression level of MAP3K3. Real-time PCR was used for RNA analysis. LncRNA-Xist silencing was done by infecting the A549 cells by lentivirus encoding shRNA which targeted the lncRNA-Xist. Results: The results showed a significant increase in the expression of lncRNA-Xist while a decrease in the miRNA103a expression (P<0.05). Silencing of lncRNA-Xist led to suppression of cell proliferation and induction of apoptosis (P<0.05). Also, lncRNA-Xist knockdown led to significant increase in expression of miRNA-103a, which in turn caused suppression of A549 cell proliferation (P<0.05). Finally, lncRNA-Xist knockdown and miR-103a overexpression independently down-regulated MAP3K3 pathway. Conclusion: lncRNA-Xist promotes progression of NSCLC by down-regulating the expression of miRNA-103a which can suppress cell proliferation and induce apoptosis and by up-regulating MAP3K3 pathway.