Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway.

作者: LELE LIN , HONGPENG JIANG , MINGKUI HUANG , XU HOU , XUEPU SUN

DOI: 10.3892/OR.2015.4010

关键词:

摘要: Overexpression of histone deacetylases (HDACs) is associated with higher metastatic rates and a poor prognosis in gastric cancer. However, the underlying mechanisms involved remain unclear. The present study aimed to investigate molecular pathways that are HDAC1-mediated activities cancer cells. First we used microRNA (miRNA or miR) microarray screen potential miRNAs whose expression can be altered by HDAC1 depletion. Of these miRNAs, miR-34a important as it often inactivated cells acts tumor suppressor for various types reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) results confirmed was upregulated knockdown. Cells depleted had lower abilities migrate, invade adhere, which were restored antagomiR. Depletion also resulted impaired microfilaments microtubules, while co-transfection antagomiR attenuated changes cellular cytoskeleton. HDAC1/miR-34a axis regulated activation CD44 its downstream factors including Bcl-2, Ras homolog family member A (RhoA), LIM domain kinase 1 (LIMK-1) matrix metalloproteinase (MMP)-2. latter three proteins responsible organization tubulin actin cytoskeleton formation pseudopodia. In conclusion, indicated depletion inhibits regulating miRNA-34a/CD44 pathway, may target treatment

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