MiR-520b restrains cell growth by targeting HDAC4 in lung cancer

miR-520b通过靶向HDAC4抑制肺癌细胞生长

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Abstract

BACKGROUND: MicroRNAs (miRNAs) function as tumor promoting or tumor suppressing factors in many cancers. MiR-520b contributes to progression in head-neck and liver cancers, spinal osteosarcoma, and glioma; however, the association of miR-520b with lung cancer progression remains unknown. In this investigation, we explore the effect of miR-520b targeting HDAC4 on lung cancer growth. METHODS: The regulation of miR-520b or its inhibitor on HDAC4 expression was analyzed using Western blot analysis. After treatment of miR-520b or its inhibitor, miR-520b and HDAC4 levels were examined using quantitative real time-PCR. The modulation of miR-520b on HDAC4 was investigated by luciferase reporter gene assay. Cell proliferation evaluation was performed using colony formation and methyl-thiazolyl-tetrazolium assays. The correlation between miR-520b and HDAC4 in human clinical samples was verified using Pearson's correlation coefficient. RESULTS: An obvious decrease in HDAC4 expression was observed in lung cancer A549 cells treated with different doses of miR-520b. The miR-520b inhibitor enhanced HDAC4 expression in lung cancer cells. Bioinformatics predicted the targeting of miR-520b on HDAC4. MiR-520b directly targeted the 3' untranslated region of HDAC4. The introduction of miR-520b obviously inhibited cell proliferation in vitro. Anti-miR-520b was capable of accelerating lung cancer cell proliferation; however, HDAC4 knockdown destroyed anti-miR-520b-induced cell proliferation. Finally, a negative correlation between miR-520b and HDAC4 was observed in clinical human lung cancer samples. CONCLUSION: MiR-520b decreases HDAC4 expression to control cell proliferation in lung cancer.

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