Zhou Chunxian, Cui Fengyun, Li Jiali, Wang Diyi, Wei Yingze, Wu Ying, Wang Jiping, Zhu Hongguang, Wang Shuyang
Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of Pathology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Oncotarget. 2017 Jul 25;8(30):49534-49547. doi: 10.18632/oncotarget.17743.
Although 5-year survival rate of non-metastatic colorectal cancer (CRC) is high, about 10% of patients in stage I and II still develop into metastatic CRC and eventually die after resection. Currently, there is no effective biomarker for predicting the prognosis of non-metastatic CRC in clinical practice. In this study, we identified miR-650 as a biomarker for prognosis prediction. We observed that the expression of miR-650 in tumor tissues had a positive association with overall survival. MiR-650 inhibited cell growth and invasion in vitro and in vivo. Furthermore, miR-650 targeted AKT2 and repressed the activation of the AKT pathway (AKT2/GSK3β/E-cadherin). Thus it induced the translocation of E-cadherin and β-catenin in cancer cells. Our results highlight the potential of miR-650 as a prognostic prediction biomarker and therapeutic target in non-metastatic CRC via inhibition of the AKT2/GSK3β/E-cadherin pathway.
尽管非转移性结直肠癌（CRC）的5年生存率较高，但I期和II期患者中仍有大约10%会发展为转移性结直肠癌，并最终在切除术后死亡。目前，在临床实践中尚无有效的生物标志物可用于预测非转移性结直肠癌的预后。在本研究中，我们鉴定出miR-650作为一种预后预测生物标志物。我们观察到，miR-650在肿瘤组织中的表达与总生存期呈正相关。miR-650在体外和体内均抑制细胞生长和侵袭。此外，miR-650靶向AKT2并抑制AKT信号通路（AKT2/GSK3β/E-钙黏蛋白）的激活。因此，它诱导癌细胞中E-钙黏蛋白和β-连环蛋白的易位。我们的结果凸显了miR-650通过抑制AKT2/GSK3β/E-钙黏蛋白信号通路，作为非转移性结直肠癌预后预测生物标志物和治疗靶点的潜力。
