miR-330调控TAp73α介导的结直肠癌细胞HCT116对顺铂的敏感性
TAp73α-mediated cisplatin sensitivity was suppressed by miR-330 in colorectal cancer cell HCT116
作者：黄玲(四川大学生命科学学院生长代谢与衰老研究中心 生物资源与生态环境教育部重点实验室)；童英(四川大学生命科学学院生长代谢与衰老研究中心 生物资源与生态环境教育部重点实验室)；肖智雄(四川大学生命科学学院生长代谢与衰老研究中心 生物资源与生态环境教育部重点实验室)；张渝君(四川大学生命科学学院生长代谢与衰老研究中心 生物资源与生态环境教育部重点实验室)
Author：HUANG Ling(Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University)；TONG Ying(Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University)；XIAO Zhi-Xiong(Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University)；ZHANG Yu-Jun(Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University)
收稿日期：2015-04-09 年卷（期）页码：2016,53(1):228-234
期刊名称：四川大学学报: 自然科学版
Journal Name：Journal of Sichuan University (Natural Science Edition)
关键字：p73；miR-330；细胞凋亡；顺铂；结肠癌
Key words：P73; MiR-330; Apoptosis; Cisplatin; Colorectal cancer
基金项目：国家自然科学基金
中文摘要
p73是p53基因家族中的一员，参与了细胞周期进程、凋亡和肿瘤耐药性等过程的调控.我们发现，在结肠癌细胞HCT116中，沉默p73可促进细胞对顺铂的敏感性，而且这种作用不依赖于p53.Hsa-miR-330 (miR-330)可直接抑制细胞内源性p73的表达并促进其对顺铂的敏感性.p73则可拮抗miR-330诱导的顺铂敏感性.我们的结果表明了p73对细胞顺铂敏感性的调控作用，为治疗顺铂抗性的肿瘤细胞提供了一条新途径.
英文摘要
The p53 family member p73 is a transcription factor involved in the regulation of cell cycle, apoptosis and cancer cell drug-resistant. Here we reported that knockdown of p73 sensitized HCT116 colorectal cancer cells to cisplatin treatment independent of p53. Hsa-miR-330 (miR-330) was identified to be able to directly repress the expression of TAp73α. Overexpression of miR-330 decreased the protein levels of endogenous TAp73α and phenocopied the effect of p73 knockdown. Restoration of TAp73α eliminated miR-330-induced chemosensitivity toward cisplatin. Our results demonstrated a novel function of TAp73α to impair cisplatin sensitivity in colorectal cancer cells which can be repressed by miR-330, thus provided an effective strategy for therapeutic treatment of cisplatin-resistant cancer cells.
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