MiR-188 inhibits proliferation and promotes apoptosis of lung adenocarcinoma cells by targeting SIX1 to negatively regulate ERK signaling pathway

D.-Q. Lv, H.-Y. Li, X.-M. Wu, L. Lin, S.-Q. Yan, Q.-Y. Guo

Department of Respiratory and Critical Medicine, Affiliated Taizhou Hospital of Zhejiang Province of Wenzhou Medical University, Taizhou, China. guoqy@enzemed.com

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• Oncology

OBJECTIVE: To explore the effects of micro ribonucleic acid (miR)-188 on proliferation and apoptosis of lung adenocarcinoma (LUAD) cells, and its potential mechanism.
MATERIALS AND METHODS: The expression level of miR-188 in LUAD cell lines was detected via quantitative Real Time-Polymerase Chain Reaction (PCR). The effects of miR-188 overexpression on proliferation and apoptosis of A549 cells were detected using methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and flow cytometry. The potential targets for miR-188 were predicted using the TargetScan Human database, and the interaction between miR-188 and target gene was determined through Dual-Luciferase reporter assay. Moreover, the associations of miR-188 and sine oculis homeobox homolog 1 (SIX1) with the extracellular signal-regulated kinase (ERK) pathway were detected via Western blotting.
RESULTS: The expression of miR-188 significantly declined in LUAD cell lines (p<0.05). The overexpression of miR-188 significantly reduced the proliferation rate of A549 cells and increased the percentage of apoptotic A549 cells (p<0.05). Similarly, it was found in colony formation assay that the overexpression of miR-188 inhibited the colony formation ability of A549 cells most significantly (p<0.05). SIX1 was a direct target for miR-188, and its mRNA and protein expressions were downregulated by the overexpression of miR-188. The remarkable downregulation of phosphorylated ERK was observed in A549 cells overexpressing miR-188, while the decline in phosphorylated ERK was reversed in A549 cells overexpressing miR-188 and SIX1.
CONCLUSIONS: The expression of miR-188 is downregulated in LUAD cell lines. The overexpression of miR-188 inhibits proliferation and promotes apoptosis of LUAD cells, whose functional mechanism may be related to its regulation on the ERK signaling pathway by targeting SIX1.

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