Background: Long noncoding RNAs (lncRNAs) have been revealed to play essential role in drug resistance of multiple cancers. LncRNA MEG3 was previously reported to be associated with cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) cells. However, the molecular mechanism of MEG3 affecting DDP resistance in NSCLC remains to be further illustrated. In this study, we attempted to discuss whether MEG3 also could function as a competing endogenous RNA to regulate DDP resistance in NSCLC.
Materials and methods: The expression of MEG3, miR-21-5p, and sex-determining region Y-box 7 (SOX7) in NSCLC tissues or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and caspase-3 activity analysis were applied to assess the DDP sensitivity of NSCLC cells. The interaction between MEG3, miR-21-5p, and SOX7 was explored by luciferase reporter assay, RNA immunoprecipitation (RIP) assay, qRT-PCR, and Western blot. Mouse NSCLC transplanted tumor was established to verify the functional role of MEG3 in DDP resistance in vivo.
Results: MEG3 was downregulated in DDP-resistant NSCLC cells. Overexpression of MEG3 enhanced DDP sensitivity of NSCLC cells in vitro. MEG3 directly interacted with miR-21-5p and suppressed its expression. miR-21-5p significantly abolished the effects of MEG3 on DDP resistance via modulating cell proliferation and apoptosis. SOX7 was identified as a direct target of miR-21-5p and MEG3 positively regulated SOX7 expression by suppressing miR-21-5p. Moreover, MEG3 knockdown-induced pro-proliferative and anti-apoptotic effects were reversed in DDP-resistant NSCLC cells by upregulating SOX7. Furthermore, upregulation of MEG3 induced sensitivity of NSCLC cells to DDP in vivo.
Conclusion: MEG3 overexpression induced DDP sensitivity of NSCLC cells by regulating miR-21-5p/SOX7 axis, shedding light on the molecular mechanism of MEG3 involved in the development of DDP resistance of NSCLC cells.
Keywords: MEG3, miR-21-5p/SOX7, DDP resistance, NSCLC