Zhou Sheng, Xiong Min, Dai Guo, Yu Ling, Zhang Zhengpei, Chen Jie, Guo Weichun
Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Department of Orthopedics, Dongfeng General Hospital, Shiyan, Hubei 442001, P.R. China.
Oncol Lett. 2018 May;15(5):6947-6956. doi: 10.3892/ol.2018.8180. Epub 2018 Mar 6.
Osteosarcoma is the most frequent primary malignant bone tumor. An increasing body of evidence has suggested that microRNAs (miRNA/miRs) have emerged as critical regulators in the initiation and progression of osteosarcoma. The present study explored the biological function of miR-192-5p and ubiquitin-specific protease 1 (USP1), and investigated whether miR-192-5p could directly interact with USP1 in osteosarcoma. The results revealed that miR-192-5p was significantly downregulated in osteosarcoma tissues and cell lines, while a reverse expression profile of USP1 was observed. Ectopic expression of miR-192-5p restrained cell proliferation, apoptosis, migration and invasion. In addition, it increased the sensitivity of osteosarcoma cells to cisplatin. USP1 was also observed to be a direct target gene of miR-192-5p in osteosarcoma. Overexpression of USP1 promoted cell proliferation, apoptosis, migration and invasion, and decreased cell chemo-sensitivity; however, it could be partially reversed via the overexpression of miR-192-5p in osteosarcoma cell lines. Taken together, the present study demonstrated that miR-192-5p suppressed the initiation and progression of osteosarcoma by targeting USP1. Therefore, miR-192-5p may serve as a valuable biomarker and the miR-192-5p/USP1 axis may function as a novel therapeutic target for osteosarcoma.
骨肉瘤是最常见的原发性恶性骨肿瘤。越来越多的证据表明,微小RNA(miRNA/miRs)已成为骨肉瘤发生和发展的关键调节因子。本研究探讨了miR-192-5p和泛素特异性蛋白酶1(USP1)的生物学功能,并研究了miR-192-5p在骨肉瘤中是否能直接与USP1相互作用。结果显示,miR-192-5p在骨肉瘤组织和细胞系中显著下调,而USP1呈现相反的表达谱。miR-192-5p的异位表达抑制了细胞增殖、凋亡、迁移和侵袭。此外,它还增加了骨肉瘤细胞对顺铂的敏感性。在骨肉瘤中,USP1也被观察到是miR-192-5p的直接靶基因。USP1的过表达促进了细胞增殖、凋亡、迁移和侵袭,并降低了细胞化学敏感性;然而,在骨肉瘤细胞系中通过miR-192-5p的过表达可部分逆转这种情况。综上所述,本研究表明miR-192-5p通过靶向USP1抑制骨肉瘤的发生和发展。因此,miR-192-5p可能作为一种有价值的生物标志物,且miR-192-5p/USP1轴可能成为骨肉瘤的新型治疗靶点。