microRNA-141 is involved in a nasopharyngeal carcinoma-related genes network

鼻咽癌 PTEN公司 生物 小RNA 癌变 癌症研究 基因敲除 抑癌基因 表观遗传学 癌症 细胞生物学 PI3K/AKT/mTOR通路 基因 遗传学 信号转导 医学 放射治疗 内科学
作者
Liming Zhang,Tan Deng,Xiayu Li,Huaying Liu,Hou‐De Zhou,Jian Ma,Minghua Wu,Ming Zhou,Shourong Shen,Xiaoling Li,Zhaoxia Niu,Wenling Zhang,Lei Shi,Bo Xiang,Jianhong Lu,Li Wang,Dan Li,Hailin Tang,Guiyuan Li
出处
期刊:Carcinogenesis [Oxford University Press]
卷期号:31 (4): 559-566 被引量:156
标识
DOI:10.1093/carcin/bgp335
摘要

microRNAs (miRNAs) are small non-coding RNAs and have been implicated in the pathology of various diseases, including cancer. Here we report that the miRNA profiles have been changed after knockdown of one of the most important oncogene c-MYC or re-expression of a candidate tumor suppressor gene SPLUNC1 in nasopharyngeal carcinoma (NPC) cells. Both c-MYC knockdown and SPLUNC1 re-expression can down-regulate microRNA-141 (miR-141). miR-141 is up-regulated in NPC specimens in comparison with normal nasopharyngeal epithelium. Inhibition of miR-141 could affect cell cycle, apoptosis, cell growth, migration and invasion in NPC cells. We found that BRD3 , UBAP1 and PTEN are potential targets of miR-141, which had been confirmed following luciferase reporter assays and western blotting. BRD3 and UBAP1 are both involved in NPC carcinogenesis as confirmed through our previous studies and PTEN is a crucial tumor suppressor in many tumor types. BRD3 is involved in the regulation of the Rb/E2F pathway. Inhibition of miR-141 could affect some important molecules in the Rb/E2F, JNK2 and AKT pathways. It is well known that carcinogenesis of NPC is involved in the networks of genetic and epigenetic alteration events. We propose that miR-141- and tumor-related genes c-MYC , SPLUNC1 , BRD3 , UBAP1 and PTEN may constitute a gene–miRNA network to contribute to NPC development.
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