Clinical and biological significance of miR-378a-3p and miR-378a-5p in colorectal cancer
Clinical and biological significance of miR-378a-3p and miR-378a-5p in colorectal cancer
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DOI：
10.1016/j.ejca.2013.12.010
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发表时间：
2014-04-01
影响因子：
8.4
通讯作者：
Han, Anjia
中科院分区：
文献类型：
--
作者：
Li, Hui;Dai, Sujuan;Han, Anjia
探讨miR-378 a-3 p和miR-378 a-5 p在结直肠癌（CRC）中的表达及其与临床病理特征的关系。我们的研究结果显示miR-378 a-3 p和miR-378 a-5 p在结直肠癌细胞系和组织中的表达分别显著低于癌旁正常结直肠粘膜组织。miR-378 a-3 p和miR-378 a-5 p的表达分别与组织分化和TNM分期显著相关。miR-378 a-3 p和miR-378 a-5 p低表达的CRC患者的生存时间分别显著短于miR-378 a-3 p和miR-378 a-5 p高表达的患者（p < 0.001，p < 0.001）。单因素和多因素考克斯回归分析显示，肿瘤大小、TNM分期、miR-378 a-3 p和miR-378 a-5 p表达是影响结直肠癌患者预后的独立因素。miR-378 a-3 p或miR-378 a-5 p的异位表达可抑制结直肠癌细胞的增殖和集落形成，诱导细胞凋亡和G1期细胞阻滞，但对结直肠癌细胞的迁移和侵袭能力无影响。miR-378 a-3 p过表达或下调可抑制或增强胰岛素样生长因子1受体（IGF 1 R）在结直肠癌细胞中的表达。IGF 1 R与miR-378 a-3 p在结直肠癌组织中的表达呈显著负相关。miR-378 a-3 p过表达或下调可抑制或增强磷酸化ERK 1/2蛋白水平，但对磷酸化Akt蛋白水平无影响。结论：miR-378 a-3 p和miR-378 a-5 p作为抑癌基因在结直肠癌的发生发展中起重要作用。(C)2013爱思唯尔有限公司保留所有权利。
To investigate miR-378a-3p and miR-378a-5p expression and their relationships with the clinicopathological features of colorectal cancer (CRC). Our results showed that miR-378a-3p and miR-378a-5p expression were dramatically lower in CRC cell lines and tissues than that in adjacent normal colorectal mucosal tissues, respectively. MiR-378a-3p and miR-378a-5p expression were significantly associated with histological differentiation and TNM stage, respectively. CRC patients with low miR-378a-3p and miR-378a-5p expression had a significantly shorter survival time than those patients with high miR-378a-3p and miR-378a-5p expression (p < 0.001, p < 0.001), respectively. Univariate and multivariable Cox regression analysis showed that tumour size, TNM stage, miR-378a-3p expression and miR-378a-5p expression were independent prognostic factors for CRC patients. Ectopic miR-378a-3p or miR-378a-5p expression inhibited cellular proliferation and colony formation, induced apoptosis and G1-phase cell cycle arrest in CRC cells, but had no effect on migration and invasion of CRC cells. Furthermore, miR-378a-3p over-expression or down-regulation could inhibit or enhance insulin-like growth factor 1 receptor (IGF1R) expression in CRC cells. There was a significantly negative correlation between IGF1R protein expression and miR-378a-3p expression in CRC tissues. MiR-378a-3p over-expression or down-regulation suppressed or enhanced phosphorylated-ERK1/2 protein level, but had no effect on phosphorylated-Akt protein level. In conclusion, miR-378a-3p and miR-378a-5p expression might play an important role as tumour suppressor gene in the initial stage of carcinogenesis of CRC. (C) 2013 Elsevier Ltd. All rights reserved.