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MicroRNA-145-3p 通过靶向 HDAC4 抑制骨肉瘤细胞的增殖,促进其凋亡和自噬。

MicroRNA-145-3p suppresses proliferation and promotes apotosis and autophagy of osteosarcoma cell by targeting HDAC4.

机构信息

a Department of Hand Surgery , China-Japan Union Hospital, Jilin University , Changchun , China.

b Department of Orthopedics , China-Japan Union Hospital, Jilin University , Changchun , China.

出版信息

Artif Cells Nanomed Biotechnol. 2018;46(sup2):579-586. doi: 10.1080/21691401.2018.1464459. Epub 2018 Jun 12.

DOI:10.1080/21691401.2018.1464459
PMID:29893594
Abstract

Studies have shown that miR-145-3p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the mechanism of a tumor suppressor of miR-145-3p. The expressions of miR-194 in osteosarcoma cell lines and tissues were monitored by real-time PCR. The proliferation ability was examined by MTT assay. The apoptosis and autophagy of cells were monitored by flow cytometry and microcopy, respectively. The regulation of miR-145-3p on HDAC4 was determined by luciferase assays and western blot assay. The results showed that miR-145-3p was significantly reduced in the osteosarcoma compared with the normal bone tissue. Overexpression of miR-145-3p significantly attenuated the proliferation and induced the apoptosis and autophagy of osteosarcoma cells. Furthermore, we demonstrated that miR-145-3p has inhibited the malignant behavior of osteosarcoma by down-regulating HDAC4 expression. These findings suggested that miR-145-3p may act as a tumor suppressor in osteosarcoma. MiR-145-3p/HDAC4 may be a novel therapeutic target in treatment of osteosarcoma.

摘要

研究表明,miR-145-3p 作为一种肿瘤抑制因子,与肿瘤的生长和转移有关。本研究旨在揭示 miR-145-3p 作为肿瘤抑制因子的作用机制。通过实时 PCR 监测骨肉瘤细胞系和组织中 miR-194 的表达。通过 MTT 测定法检测细胞的增殖能力。通过流式细胞术和显微镜分别监测细胞的凋亡和自噬。通过荧光素酶测定法和 Western blot 分析确定 miR-145-3p 对 HDAC4 的调节。结果表明,与正常骨组织相比,骨肉瘤中 miR-145-3p 的表达明显降低。miR-145-3p 的过表达显著减弱了骨肉瘤细胞的增殖,并诱导了细胞的凋亡和自噬。此外,我们证明 miR-145-3p 通过下调 HDAC4 表达抑制了骨肉瘤的恶性行为。这些发现表明,miR-145-3p 可能在骨肉瘤中发挥肿瘤抑制作用。miR-145-3p/HDAC4 可能成为骨肉瘤治疗的新靶点。

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