4.5 Article

miR-181b inhibits chemoresistance in cisplatin-resistant H446 small cell lung cancer cells by targeting Bcl-2

Journal

ARCHIVES OF MEDICAL SCIENCE
Volume 14, Issue 4, Pages 745-751

Publisher

TERMEDIA PUBLISHING HOUSE LTD
DOI: 10.5114/aoms.2018.73131

Keywords

miR-181b; small cell lung cancer cells; Bcl-2; cisplatin-resistant

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Introduction: MicroRNAs (miRNAs) are a group of small non-coding RNAs that affect multiple aspects of tumor biology including chemo resistance. miR-181b has been reported to modulate multidrug resistance in non-small cell lung cancer cells. This study was undertaken to determine the role of miR-181b in chemo resistance of small cell lung cancer cells. Material and methods: This study was undertaken to determine the role of miR-181b in chemoresistance of small cell lung cancer cells with use of qRt-PCR, WB, bioinformatics analysis, and double luciferase reporter system. Results: Our data showed that miR-181b was significantly downregulated in cisplatin-resistant H446 small cell lung cancer cells, compared to parental cells, compared to parental cells. Ectopic expression of miR-181b inhibited cell proliferation and invasion in cisplatin-resistant H446 cells (p = 0.023). Moreover, overexpression of miR-181b increased the susceptibility of cisplatin-resistant H446 cells to cisplatin. Mechanistic investigations demonstrated that miR-181b inhibited B-cell lymphoma-2 (Bcl-2) expression by binding to the 3'-untranslated region. Overexpression of Bcl-2 reversed miR-181b-mediated chemo sensitization, which is accompanied by a reduced apoptotic response. Conclusions: Taken together, this work demonstrated that miR-181b might have the ability to overcome chemo resistance of small cell lung cancer cells, and restoration of this miRNA may represent a potential therapeutic strategy for improving chemo sensitivity in small cell lung cancer.

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