Wang Yadong, Zhang Shanfeng, Xu Yan, Zhang Yan, Guan Hongya, Li Xinjie, Li Yuebai, Wang Yisheng
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, 100 Kexue Road, Zhengzhou, 450001, China.
Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, China.
Tumour Biol. 2016 Nov;37(11):15211-15220. doi: 10.1007/s13277-016-5417-z. Epub 2016 Sep 28.
MicroRNAs (miRNAs) can function as oncogenes or tumor suppressor genes and are involved in multiple processes in cancer development and progression. For example, miR-192 is dysregulated in multiple human cancers, including osteosarcoma (OS). However, the pathophysiological role of miR-192 and its relevance to OS cell growth and invasion has not yet been clarified. This study aimed to investigate the expression of miR-192 in OS and elucidate the molecular mechanisms by which miR-192 acts as a tumor suppressor in this disease. The qRT-PCR data identified significant down-regulation of miR-192 in 20 OS tissue samples and two OS cell lines when compared with adjacent normal tissues and a human osteoblast cell line, respectively. Furthermore, Western blot analysis revealed overexpression of T cell-specific transcription factor (TCF) 7 protein in tumor tissues compared with matched adjacent normal tissues. Further in vitro studies demonstrated that enforced expression of miR-192 inhibited U2OS and MG63 cell proliferation, invasion, and migration and induced apoptosis. Finally, Western blot and Luciferase assays identified TCF7 as a target of miR-192. Collectively, these findings suggest an important role for miR-192 in regulating the proliferation, migration, invasion, and apoptosis of OS cells through the regulation of TCF7.
微小RNA(miRNA)可作为癌基因或肿瘤抑制基因发挥作用,并参与癌症发生和发展的多个过程。例如,miR-192在包括骨肉瘤(OS)在内的多种人类癌症中表达失调。然而,miR-192的病理生理作用及其与OS细胞生长和侵袭的相关性尚未阐明。本研究旨在探讨miR-192在OS中的表达,并阐明miR-192在该疾病中作为肿瘤抑制因子发挥作用的分子机制。qRT-PCR数据显示,与相邻正常组织和人成骨细胞系相比,20例OS组织样本和两种OS细胞系中miR-192均显著下调。此外,蛋白质印迹分析显示,与匹配的相邻正常组织相比,肿瘤组织中T细胞特异性转录因子(TCF)7蛋白表达上调。进一步的体外研究表明,miR-192的强制表达抑制了U2OS和MG63细胞的增殖、侵袭和迁移,并诱导了细胞凋亡。最后,蛋白质印迹和荧光素酶测定确定TCF7是miR-192的靶标。总之,这些发现表明miR-192通过调节TCF7在调控OS细胞的增殖、迁移、侵袭及凋亡中发挥重要作用。