微小RNA-194通过靶向钙黏蛋白2(CDH2)和胰岛素样生长因子1受体(IGF1R)在体外和体内抑制骨肉瘤细胞的增殖和转移。

microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R.

作者信息

Han Kang, Zhao Tingbao, Chen Xiang, Bian Na, Yang Tongtao, Ma Qiong, Cai Chengkui, Fan Qingyu, Zhou Yong, Ma Baoan

机构信息

Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.

Department of Spinal Cord Injury, General Hospital of Jinan Military Area Command of Chinese PLA, Jinan, Shandong, P.R. China.

出版信息

Int J Oncol. 2014 Oct;45(4):1437-49. doi: 10.3892/ijo.2014.2571. Epub 2014 Jul 30.

Abstract

Studies have shown that miR-194 functions as a tumor suppressor and is associated with tumor growth and metastasis. We studied the effects of miR-194 in osteosarcoma and the possible mechanism by which miR-194 affected the survival, apoptosis and metastasis of osteosarcoma. Both human osteosarcoma cell lines SOSP-9607 and U2-OS were transfected with recombinant lentiviruses to regulate miR-194 expression. Overexpression of miR-194 partially inhibited the proliferation, migration, and invasion of osteosarcoma cells in vitro, as well as tumor growth and pulmonary metastasis of osteosarcoma cells in vivo. Potential miR-194 target genes were predicted using bioinformatics. Luciferase reporter assay, real-time quantitative PCR and western blotting confirmed that CDH2 (N-cadherin) and IGF1R were targets of miR-194. Using real-time quantitative PCR, we evaluated the expression of miR-194 and two miR-194 target genes, CDH2 and IGF1R in osteosarcoma samples from 107 patients and 99 formalin- or paraformalin-fixed paraffin-embedded tissues. The expressions of the target genes were also examined in osteosarcoma samples using immunohistochemistry. Overexpression of miR-194 inhibited tumor growth and metastasis of osteosarcoma probably by downregulating CDH2 and IGF1R. miR-194 may prove to be a promising therapeutic agent for osteosarcoma.

摘要

研究表明,miR-194发挥肿瘤抑制作用,并与肿瘤生长和转移相关。我们研究了miR-194在骨肉瘤中的作用以及miR-194影响骨肉瘤生存、凋亡和转移的可能机制。用重组慢病毒转染人骨肉瘤细胞系SOSP-9607和U2-OS以调节miR-194表达。miR-194的过表达在体外部分抑制了骨肉瘤细胞的增殖、迁移和侵袭,以及在体内抑制了骨肉瘤细胞的肿瘤生长和肺转移。使用生物信息学预测潜在的miR-194靶基因。荧光素酶报告基因检测、实时定量PCR和蛋白质印迹证实CDH2(N-钙黏蛋白)和IGF1R是miR-194的靶标。我们使用实时定量PCR评估了107例患者的骨肉瘤样本以及99例福尔马林或多聚甲醛固定石蜡包埋组织中miR-194和两个miR-194靶基因CDH2和IGF1R的表达。还使用免疫组织化学在骨肉瘤样本中检测了靶基因的表达。miR-194的过表达可能通过下调CDH2和IGF1R来抑制骨肉瘤的肿瘤生长和转移。miR-194可能被证明是一种有前途的骨肉瘤治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2765/4151797/8e3b954eace5/IJO-45-04-1437-g00.jpg

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