Department of Pathology, The Shenzhen University School of Medicine, Shenzhen, Guangdong, 518060, China.
Shenzhen Key Laboratory of Micromolecule Innovatal Drugs, Shenzhen Key Laboratory of translational Medicine of Tumor, Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University School of Medicine, Shenzhen, Guangdong, China.
Cancer Med. 2018 Jan;7(1):146-156. doi: 10.1002/cam4.1237. Epub 2017 Dec 13.
SMG-1,a member of the phosphoinositide kinase-like kinase family, functioned as a tumor suppressor gene. However, the role of SMG-1 in GC remain uncharacterized. In this study, regulation of SMG-1 by miR-192 and-215, along with the biological effects of this modulation, were studied in GC. We used gene microarrays to screening and luciferase reporter assays were to verify the potential targets of miR-192 and-215. Tissue microarrays analyses were applied to measure the levels of SMG-1 in GC tissues. Western blot assays were used to assess the signaling pathway of SMG-1 regulated by miR-192 and-215 in GC. SMG-1 was significantly downregulated in GC tissues.The proliferative and invasive properties of GC cells were decreased by inhibition of miR-192 and-215, whereas an SMG-1siRNA rescued the inhibitory effects. Finally, SMG-1 inhibition by miR-192 and-215 primed Wnt signaling and induced EMT. Wnt signaling pathway proteins were decreased markedly by inhibitors of miR-192 and-215, while SMG-1 siRNA reversed the inhibition apparently. Meanwhile, miR-192 and-215 inhitibtors increased E-cadherin expression and decreased N-cadherin and cotransfection of SMG-1 siRNA reversed these effects. In summary, these findings illustrate that SMG-1 is suppressed by miR-192 and-215 and functions as a tumor suppressor in GC by inactivating Wnt signaling and suppressing EMT.
SMG-1 是磷酸肌醇激酶样激酶家族的一员，作为一种肿瘤抑制基因发挥作用。然而，SMG-1 在 GC 中的作用尚不清楚。在这项研究中，研究了 miR-192 和-215 对 SMG-1 的调控及其在 GC 中的生物学效应。我们使用基因微阵列筛选，并用荧光素酶报告基因实验验证了 miR-192 和-215 的潜在靶基因。组织微阵列分析用于测量 GC 组织中 SMG-1 的水平。Western blot 检测用于评估 SMG-1 在 GC 中受 miR-192 和-215 调控的信号通路。GC 组织中 SMG-1 明显下调。抑制 miR-192 和-215 可降低 GC 细胞的增殖和侵袭能力，而 SMG-1 siRNA 则可挽救这种抑制作用。最后，miR-192 和-215 通过激活 Wnt 信号通路诱导 EMT 而抑制 SMG-1。miR-192 和-215 的抑制剂显著降低了 Wnt 信号通路蛋白的表达，而 SMG-1 siRNA 则明显逆转了这种抑制作用。同时，miR-192 和-215 抑制剂增加了 E-钙黏蛋白的表达，降低了 N-钙黏蛋白的表达，共转染 SMG-1 siRNA 则逆转了这些作用。综上所述，这些发现表明，SMG-1 受 miR-192 和-215 抑制，并通过抑制 Wnt 信号通路和 EMT 发挥肿瘤抑制作用。
