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MicroRNA-152 通过依赖于 DKK1 的方式直接靶向 Wnt/β-catenin 信号通路抑制骨肉瘤细胞增殖。

MicroRNA-152 inhibits cell proliferation of osteosarcoma by directly targeting Wnt/β-catenin signaling pathway in a DKK1-dependent manner.

机构信息

Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China.

Department of Orthopedics, Songyuan Integrated Traditional Chinese and Western Medicine Hospital, Songyuan, Jilin, P.R. China.

出版信息

Oncol Rep. 2018 Aug;40(2):767-774. doi: 10.3892/or.2018.6456. Epub 2018 May 22.

Abstract

The function of microRNA‑152 for a cohort of patients with osteosarcoma and the influence on cell growth of osteosarcoma were studied. The expression of microRNA‑152 was downregulated in patients with osteosarcoma. The downregulation of microRNA‑152 promotes cell proliferation, decreases apoptosis, and suppresses LDH activity, caspase-3/9 activities and Bax/Bcl-2 and p53 protein expression levels of osteosarcoma through activation of the Wnt/β-catenin signaling pathway by targeting DKK1. Whereas, overexpression of microRNA‑152 targets DKK1 to inhibit cell proliferation, induce apoptosis, and promote LDH activity, caspase-3/9 activities and Bax/Bcl-2 and p53 protein expression levels of osteosarcoma through inactivation of the Wnt/β-catenin signaling pathway. The promotion of DKK1 reversed the anticancer function of microRNA‑152 over-expression through Wnt/β-catenin signaling pathway. We demonstrated that microRNA‑152 inhibits cell proliferation of osteosarcoma through DKK1 by directly targeting Wnt/β‑catenin signaling pathway.

摘要

研究了 microRNA-152 对一组骨肉瘤患者的功能及其对骨肉瘤细胞生长的影响。骨肉瘤患者的 microRNA-152 表达下调。microRNA-152 的下调通过靶向 DKK1 激活 Wnt/β-catenin 信号通路,促进细胞增殖,减少细胞凋亡,抑制乳酸脱氢酶(LDH)活性、半胱天冬酶-3/9 活性以及 Bax/Bcl-2 和 p53 蛋白表达水平。而 microRNA-152 的过表达通过失活 Wnt/β-catenin 信号通路靶向 DKK1 抑制细胞增殖,诱导细胞凋亡,促进 LDH 活性、半胱天冬酶-3/9 活性以及 Bax/Bcl-2 和 p53 蛋白表达水平。DKK1 的促进作用通过 Wnt/β-catenin 信号通路逆转了 microRNA-152 过表达的抗癌功能。我们证明了 microRNA-152 通过直接靶向 Wnt/β-catenin 信号通路抑制骨肉瘤细胞的增殖。

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