Li Taiyuan, Tang Cheng, Huang Zhixiang, Yang Lingling, Dai Hua, Tang Bo, Xiao Benping, Li Jianfeng, Lei Xiong
Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.
Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China.
Aging (Albany NY). 2021 Jul 5;13(13):17349-17369. doi: 10.18632/aging.203225.
miR-144-3p is aberrantly expressed in several types of human cancer and functions as a tumor suppressor by inhibiting metastasis. However, the clinical significance and biological function of miR-144-3p in colorectal adenocarcinoma (CRA) have yet to be elucidated. Here we reported that miR-144-3p expression level was significantly down-regulated in CRA tissues compared with matched noncancerous colorectal mucosae tissues. Low miR-144-3p expression was correlated with adverse clinicopathologic characteristics and poor prognosis of CRA patients. Cox regression analysis showed that low miR-144-3p expression was an independent risk factor for DFS and OS in CRA. and assays showed that miR-144-3p significantly inhibited proliferation, migration and invasion of CRA cells. In particular, miR-144-3p could suppress EMT process of CRA cells by regulating the cytoskeleton and EMT markers. Bioinformatics analysis indicated that EMT associated transcription factors ZEB1 and ZEB2 were potential targets of miR-144-3p, and miR-144-3p inhibited ZEB1 and ZEB2 expression and was negatively correlated with their expression in CRA. Finally, we confirmed that ZEB1 and ZEB2 down-regulation collaboratively mediated the inhibitory effect of miR-144-3p on proliferation, invasion and EMT of CRA cells. In conclusion, our study provided evidence that miR-144-3p could inhibit CRA cell proliferation, invasion and EMT by targeting ZEB1/2.
miR-144-3p在多种人类癌症中异常表达,并通过抑制转移发挥肿瘤抑制作用。然而,miR-144-3p在结直肠癌(CRA)中的临床意义和生物学功能尚未阐明。在此我们报告,与配对的非癌性结直肠黏膜组织相比,CRA组织中miR-144-3p表达水平显著下调。miR-144-3p低表达与CRA患者不良的临床病理特征及预后不良相关。Cox回归分析表明,miR-144-3p低表达是CRA患者无病生存期(DFS)和总生存期(OS)的独立危险因素。 实验和 实验表明,miR-144-3p显著抑制CRA细胞的增殖、迁移和侵袭。特别是,miR-144-3p可通过调节细胞骨架和上皮-间质转化(EMT)标志物来抑制CRA细胞的EMT过程。生物信息学分析表明,EMT相关转录因子ZEB1和ZEB2是miR-144-3p的潜在靶点,且miR-144-3p抑制ZEB1和ZEB2表达,并与它们在CRA中的表达呈负相关。最后,我们证实ZEB1和ZEB2的下调共同介导了miR-144-3p对CRA细胞增殖、侵袭和EMT的抑制作用。总之,我们的研究提供了证据表明miR-144-3p可通过靶向ZEB1/2抑制CRA细胞增殖、侵袭和EMT。