Liu Zhao, Yan Yan, Cao Sizhe, Chen Yi
Department of Surgery, Xi'an Chest Hospital, Xi'an TB&Thoracic Tumor Hospital, Xi'an, Shanxi, China.
Institute of Cancer Research, School of Basic Medical Science of Xi'an Jiao Tong University, Xi'an, Shaanxi, China.
J Cell Biochem. 2018 Aug;119(8):6905-6913. doi: 10.1002/jcb.26889. Epub 2018 Apr 18.
This study aimed to elucidate the roles of long non-coding RNA SNHG14 in gastric cancer development. LncRNA SNHG14 was markedly up-regulated in gastric cancer tissues and cells. Knockdown of SNHG14 significantly inhibited SGC-7901 cell viability, migration, invasion, and promoted cell apoptosis. In addition, miR-145 was negatively regulated by SNHG14 and the effects of SNHG14 knockdown on cell viability, apoptosis, migration, invasion, and the expression of apoptosis-related proteins and EMT-markers were reversed by inhibition of miR-145 at the same time. Furthermore, SOX9 was verified as a functional target of miR-145, and miR-145 regulated tumor malignant behaviors through regulating SOX9. Besides, knockdown of SNHG14 inhibited the expression of p-PI3 K, p-AKT, and p-mTOR and promoted PTEN expression, where miR-145 inhibition had opposite effects. Moreover, the activated PI3 K/AKT/mTOR pathway caused by miR-145 inhibition was counteracted after knockdown of SOX9. Our findings indicate that up-regulation of lncRNA SNHG14 may contribute to gastric cancer development via targeting miR-145/SOX9 axis and involving in PI3 K/AKT/mTOR pathway. SNHG14-miR-145/SOX9 axis may be a promising therapeutic strategy for gastric cancer treatment.
本研究旨在阐明长链非编码RNA SNHG14在胃癌发生发展中的作用。长链非编码RNA SNHG14在胃癌组织和细胞中显著上调。敲低SNHG14可显著抑制SGC-7901细胞的活力、迁移和侵袭，并促进细胞凋亡。此外，miR-145受SNHG14负调控，同时抑制miR-145可逆转敲低SNHG14对细胞活力、凋亡、迁移、侵袭以及凋亡相关蛋白和上皮间质转化标志物表达的影响。此外，SOX9被证实为miR-145的功能靶点，miR-145通过调控SOX9来调节肿瘤的恶性行为。此外，敲低SNHG14可抑制p-PI3 K、p-AKT和p-mTOR的表达并促进PTEN表达，而抑制miR-145则产生相反的效果。而且，敲低SOX9后可抵消由抑制miR-145所激活的PI3 K/AKT/mTOR信号通路。我们的研究结果表明，lncRNA SNHG14的上调可能通过靶向miR-145/SOX9轴并参与PI3 K/AKT/mTOR信号通路促进胃癌的发生发展。SNHG14-miR-145/SOX9轴可能是一种有前景的胃癌治疗策略。
