Chae Dong-Kyu, Ban Eunmi, Yoo Young Sook, Kim Eunice EunKyeong, Baik Ja-Hyun, Song Eun Joo
Molecular Recognition Research Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, South Korea.
School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
Mol Carcinog. 2017 Aug;56(8):1992-1998. doi: 10.1002/mc.22655. Epub 2017 Apr 13.
The transforming growth factor-β (TGF-β) signaling pathway is associated with carcinogenesis and various biological processes. SMAD2 and SMAD4, which are putative tumor suppressors, have an important role in TGF-β signaling. The aberrant expression of these genes is implicated in some cancers. However, the mechanisms of SMAD2 and SMAD4 dysregulation are poorly understood. In this study, we observed that miR-27a was upregulated in lung cancer cell lines and patients. In addition, SMAD2 and SMAD4 genes were identified as targets of miR-27a by several target prediction databases and experimental validation. Functional studies revealed that miR-27a overexpression decreased SMAD2 and SMAD4 mRNA and protein levels. Furthermore, miR-27a contributed to cell proliferation and invasion by inhibiting TGF-β-induced cell cycle arrest. These results suggest that miR-27a may function as an oncogene by regulating SMAD2 and SMAD4 in lung cancer. Thus, miR-27a may be a potential target for cancer therapy.
转化生长因子-β（TGF-β）信号通路与癌症发生及多种生物学过程相关。SMAD2和SMAD4被认为是肿瘤抑制因子，在TGF-β信号传导中起重要作用。这些基因的异常表达与某些癌症有关。然而，SMAD2和SMAD4失调的机制尚不清楚。在本研究中，我们观察到miR-27a在肺癌细胞系和患者中上调。此外，通过多个靶标预测数据库和实验验证，确定SMAD2和SMAD4基因是miR-27a的靶标。功能研究表明，miR-27a过表达降低了SMAD2和SMAD4的mRNA和蛋白质水平。此外，miR-27a通过抑制TGF-β诱导的细胞周期停滞促进细胞增殖和侵袭。这些结果表明，miR-27a可能通过调节肺癌中的SMAD2和SMAD4发挥癌基因作用。因此，miR-27a可能是癌症治疗的潜在靶点。
