Huang Jianghong, Liang Yujie, Xu Meiquan, Xiong Jianyi, Wang Daping, Ding Qiang
Department of Orthopedics, Shenzhen Second People's Hospital, The First Hospital Affiliated to Shenzhen University, Shenzhen, Guangdong 518035, P.R. China.
Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Second People's Hospital, The First Hospital Affiliated to Shenzhen University, Shenzhen, Guangdong 518035, P.R. China.
Oncol Lett. 2018 Apr;15(4):4979-4987. doi: 10.3892/ol.2018.7994. Epub 2018 Feb 8.
The aim of the present study was to investigate the clinical significance of hsa-microRNA-124-3p (miR-124) in osteosarcoma (OS), and examine its role in cell growth and invasion. Using a microRNA chip array, the expression of miR-124 was detected in samples of surgically resected OS and matched against the levels of expression in tumor-adjacent normal tissues. The levels of miR-124 were upregulated in the OS cells through the transfection of miR-124 mimics. Cell proliferation and Transwell assays were performed to determine cell proliferation and invasion; Reverse transcription-quantitative polymerase chain reaction, western blot and luciferase assays were then used to detect the expression of the target gene snail family zinc finger 2 (Snail2). The expression of miR-124 was significantly lower in the OS tissues, compared with that in the tumor-adjacent normal tissues; and the expression of miR-124 in the tumor tissues was significantly associated with tumor size. miR-124 directly repressed the expression of Snail2, and resulted in a significant inhibition of cell proliferation and invasion. In a mouse model, the overexpression of miR-124 significantly inhibited U2OS cell proliferation and invasion. Taken together, miR-124 was associated with the adverse clinical and pathological features observed in OS. It acted as a tumor suppressor to regulate the proliferation and invasion of OS cells by targeting Snail2, suggesting that miR-124 may be key in the progression of OS.
本研究旨在探讨人源微小RNA-124-3p（miR-124）在骨肉瘤（OS）中的临床意义，并研究其在细胞生长和侵袭中的作用。通过微小RNA芯片阵列检测手术切除的OS样本中miR-124的表达，并与肿瘤旁正常组织中的表达水平进行对比。通过转染miR-124模拟物上调OS细胞中miR-124的水平。进行细胞增殖和Transwell实验以确定细胞增殖和侵袭能力；随后采用逆转录定量聚合酶链反应、蛋白质免疫印迹和荧光素酶实验检测靶基因锌指蛋白Snail家族成员2（Snail2）的表达。与肿瘤旁正常组织相比，OS组织中miR-124的表达显著降低；且肿瘤组织中miR-124的表达与肿瘤大小显著相关。miR-124直接抑制Snail2的表达，从而显著抑制细胞增殖和侵袭。在小鼠模型中，miR-124的过表达显著抑制U2OS细胞的增殖和侵袭。综上所述，miR-124与OS中观察到的不良临床和病理特征相关。它作为一种肿瘤抑制因子，通过靶向Snail2调节OS细胞的增殖和侵袭，提示miR-124可能在OS进展中起关键作用。
