MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition

Z. Jin, L. Guan, Y. Song, G.-M. Xiang, S.-X. Chen, B. Gao

Institute of Respiratory Disease, China Three Gorges University, Yichang Central People’s Hospital, China. 222xiaozhao@163.com

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• Oncology

OBJECTIVE: Down-regulation of miR-138 is observed in a variety of cancers, which suggests that miR-138 may be involved in cancer pathogenesis. Our current work aimed to evaluate the effects of miR-138 in adriamycin (ADM)-resistant human NSCLC cells.

MATERIALS AND METHODS: Cell proliferation was determined by MTT assay. Real-time PCR and western blot were performed to detect the mRNA and protein expression levels. The target of miR-138 was validated by luciferase activity assay.

RESULTS: Compared with the chemosensitive parental cells, miR-138 was remarkably decreased in A549/ADM and NCI-H23/ADM cells. Ectopic expression of miR-138 sensitized chemoresistant tumor cells to ADM administration. In addition, the epithelial-mesenchymal transition (EMT) related markers E-cadherin or vimentin was up-regulated or down-regulated upon the overexpression of miR-138 in NSCLC cells. Further studies identified zinc finger E-box-binding homeobox 2 (ZEB2) as the target of miR-138 and up-regulation of miR-138 suppressed the mRNA and protein expression of ZEB2. Notably, luciferase reporter assay confirmed that ZEB2 was a direct target of miR-138.

CONCLUSIONS: Our study demonstrates that miR-138 sensitizes NSCLC cells to ADM via EMT, suggesting that miR-138 might be a potential therapeutic target for drug-resistant NSCLC patients.

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