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

Abstract:

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.

authors

Jin Z,Guan L,Song Y,Xiang GM,Chen SX,Gao B

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

1080-6

issue

6

eissn

1128-3602

issn

2284-0729

journal_volume

20

pub_type

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