Clinical and biological significance of miR-193a-3p targeted KRAS in colorectal cancer pathogenesis
Clinical and biological significance of miR-193a-3p targeted KRAS in colorectal cancer pathogenesis
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DOI：
10.1016/j.humpath.2017.10.024
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发表时间：
2018-01-01
期刊：
影响因子：
3.3
通讯作者：
Lam, Alfred King-yin
中科院分区：
文献类型：
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作者：
Mamoori, Afraa;Wahab, Riajul;Lam, Alfred King-yin
本研究旨在探讨miR-193a-3p在结直肠癌中的表达模式、表达机制及临床病理意义。前瞻性地收集了70例匹配的结直肠腺癌和邻近的非肿瘤性粘膜的新鲜冷冻组织。两种结直肠癌细胞系（SW480和SW48）和一种非肿瘤性结肠细胞系（FHC）也被使用。采用实时定量聚合酶链反应检测细胞和组织中miR193a-3p的表达水平。通过免疫组织化学研究KRAS蛋白作为miR-193a的预测下游靶点的表达。通过永久转染实现了细胞系中miR-193a水平的恢复，并进行了多项功能和免疫学实验来分析miR-193a在体外的功能。与非肿瘤性结直肠癌组织相比，70%的结直肠癌组织中miR-193a-3p表达下调。此外，miR-193a的下调与早期癌的发生有显著相关性（P < 0.05）。miR-193a-3p与其靶KRAS蛋白呈显著负相关（P < 0.05）。在结肠癌细胞中过表达miR-193a导致细胞增殖减少，凋亡增加，细胞周期事件发生显著变化，上皮-间质转化标志物TWIST表达降低。本研究证实了miR-193a-3p在结直肠癌患者中的抑瘤作用及其对KRAS的下游靶点亲和力及其临床意义。(C) 2017爱思唯尔公司版权所有。
This study was to investigate the expression pattern, mechanisms and clinicopathological implications of miR-193a-3p in colorectal cancer. Fresh-frozen tissues from 70 matched colorectal adenocarciomas and the adjacent non-neoplastic mucosae were prospectively collected. Two colorectal cancer cell lines (SW480 and SW48) and a non-neoplastic colon cell line (FHC) were also used. The expression levels of miR193a-3p in the cells and tissues were measured by quantitative real-time polymerase chain reaction. The expression of KRAS protein as a predicted downstream target for miR-193a was studied by immunohistochemistry. Restoration of the miR-193a level in the cell lines by permanent transfection was achieved and multiple functional and immunological assays were performed to analyze the functions of miR-193a in vitro. Down-regulation of miR-193a-3p was noted in 70% of the colorectal cancer tissues when compared to non-neoplastic colorectal tissues. In addition, down-regulation of miR-193a was significantly correlated with carcinoma of early stages (P < .05). Significant inverse correlation between miR-193a-3p and its target KRAS protein was determined (P < .05). Overexpression of miR-193a in colon cancer cells resulted in reduced cell proliferation, increased apoptosis, induced significant changes in cell cycle events and decreased the expression of epithelial-mesenchymal transition marker TWIST. This study confirms the tumor suppressor roles of miR-193a-3p, its downstream target affinity to KRAS and clinical significance in patients with colorectal adenocarcinoma. (C) 2017 Elsevier Inc. All rights reserved.