Shang Guowei, Mi Yang, Mei Yingwu, Wang Guanghui, Wang Yadong, Li Xinjie, Wang Yisheng, Li Yuebai, Zhao Guoqiang
Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
Oncol Lett. 2018 May;15(5):7265-7272. doi: 10.3892/ol.2018.8239. Epub 2018 Mar 12.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during stem cell growth, proliferation and differentiation. miRNAs are also involved in the development and progression of a number of cancer types, including osteosarcoma (OS). miR-192 is significantly downregulated in various tumors, including lung, bladder and rectal cancer. miR-192 expression is associated with the migration and invasion of OS cells. However, the expression of miR-192 and its effects on the development of OS have not been reported. In the present study, the involvement of miR-192 and its molecular mechanisms in the development of OS was investigated. The results indicate that miR-192 expression was significantly downregulated in OS tissues compared with non-tumor tissues (P<0.05). Next, a miR-192 agomir was transfected into the OS cell line MG-63 to upregulate miR-192. The effects of miR-192 overexpression were then investigated by examining cell proliferation, apoptosis, migration and invasion. Matrix metalloproteinase (MMP)-11 belongs to a family of nine or more highly homologous Zn-endopeptidases. It was demonstrated that the mRNA and protein expression of MMP-11 were upregulated in OS tissues compared with non-tumor tissues (P<0.05). MMP-11 was predicted by TargetScan and miRanda as a miR-192 target, which was confirmed by western blotting and dual-luciferase assays. Finally, it was demonstrated that the overexpression of miR-192 was able to downregulate MMP-11 expression and reduce proliferation, migration and invasion, and promote apoptosis in OS cells. Together, these data indicate that miR-192 may be a tumor suppressor that inhibits the progression and invasion of OS by targeting MMP-11. Therefore, miR-192 may be useful for the diagnosis and treatment of OS.
微小RNA（miRNA）是一类小的非编码RNA，在干细胞生长、增殖和分化过程中调控基因表达。miRNA还参与多种癌症类型的发生和发展，包括骨肉瘤（OS）。miR-192在包括肺癌、膀胱癌和直肠癌在内的多种肿瘤中显著下调。miR-192的表达与OS细胞的迁移和侵袭相关。然而，miR-192的表达及其对OS发生发展的影响尚未见报道。在本研究中，对miR-192及其分子机制在OS发生发展中的作用进行了研究。结果表明，与非肿瘤组织相比，OS组织中miR-192的表达显著下调（P<0.05）。接下来，将miR-192激动剂转染到OS细胞系MG-63中以上调miR-192。然后通过检测细胞增殖、凋亡、迁移和侵袭来研究miR-192过表达的影响。基质金属蛋白酶（MMP）-11属于一个由九个或更多高度同源的锌内肽酶组成的家族。结果表明，与非肿瘤组织相比，OS组织中MMP-11的mRNA和蛋白表达上调（P<0.05）。通过TargetScan和miRanda预测MMP-11是miR-192的靶标，蛋白质免疫印迹法和双荧光素酶报告基因检测证实了这一点。最后，结果表明miR-192的过表达能够下调MMP-11的表达，并减少OS细胞的增殖、迁移和侵袭，促进其凋亡。总之，这些数据表明miR-192可能是一种肿瘤抑制因子，通过靶向MMP-11抑制OS的进展和侵袭。因此，miR-192可能对OS的诊断和治疗具有重要意义。
