CircLRP6 Regulation of ZEB1 via miR-455 Is Involved in the Epithelial-Mesenchymal Transition During Arsenite-Induced Malignant Transformation of Human Keratinocytes

被引：43

作者：

Xue, Junchao ^{[1
,2
]}

Chen, Chao ^{[1
,2
]}

Luo, Fei ^{[1
,2
]}

Pan, Xueli ^{[3
]}

Xu, Hui ^{[1
,2
]}

Yang, Ping ^{[4
]}

Sun, Qian ^{[1
,2
]}

Liu, Xinlu ^{[1
,2
]}

Lu, Lu ^{[1
,2
]}

Yang, Qianlei ^{[1
,2
]}

Xiao, Tian ^{[1
,2
]}

Dai, Xiangyu ^{[1
,2
]}

Luo, Peng ^{[3
]}

Lu, Jiachun ^{[4
]}

Zhang, Aihua ^{[3
]}

Liu, Qizhan ^{[1
,2
]}

机构：

[1] Nanjing Med Univ, Sch Publ Hlth, Inst Toxicol, Nanjing 211166, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing 211166, Jiangsu, Peoples R China

[3] Guizhou Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Environm Pollut Monitoring & Dis Control, Guiyang 550025, Guizhou, Peoples R China

[4] Guangzhou Med Univ, Inst Chem Carcinogenesis, Sch Publ Hlth, Guangzhou 510182, Guangdong, Peoples R China

来源：

TOXICOLOGICAL SCIENCES | 2018年 / 162卷 / 02期

关键词：

circRNAs; miRNAs; EMT; carcinogenesis; arsenite; CIRCULAR RNAS; OXIDATIVE STRESS; CANCER; PROMOTES; CELLS; IDENTIFICATION; PROGRESSION; EXPRESSION; CARCINOGENESIS; TUMORIGENESIS;

D O I：

10.1093/toxsci/kfx269

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Circular RNAs (circRNAs), a class of noncoding RNAs generated from pre-mRNAs, participate in the regulation of tumorigenesis. The mechanism for regulation, however, is unclear. Here, to determine whether circRNAs are involved in arsenite-induced epithelial-mesenchymal transition (EMT) and malignant transformation in human keratinocyte (HaCaT) cells, the up-regulation of circLRP6 was confirmed in arsenite-transformed HaCaT (T-HaCaT) cells. In HaCaT cells, circLRP6 acted as an microRNA (miR)-455 sponge. For these cells, chronic exposure to arsenite caused an increase of circLRP6 and the transcription factor ZEB1, which induced the EMT. miR-455 suppressed the expression of ZEB1. Further, in T-HaCaT cells, knockdown of circLRP6 with siRNA inhibited ZEB1 expression, but cotransfection with circLRP6 siRNA and an miR-455 inhibitor reversed this inhibition. These results suggest that, in HaCaT cells, arsenite increases circLRP6 levels, which act as a sponge for miR-455 and up-regulate the miR-455 target, ZEB1, which subsequently induces the EMT, thus promoting malignant transformation. Thus, for HaCaT cells chronically exposed to arsenite, circLRP6 via miR-455 regulation of ZEB1 is involved in the EMT during malignant transformation. The results establish a previously unknown mechanism for arsenite-induced carcinogenesis.

引用

页码：450 / 461

页数：12

共 53 条

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