Methylseleninic acid activates Keap1/Nrf2 pathway via up-regulating miR-200a in human oesophageal squamous cell carcinoma cells

被引：32

作者：

Liu, Mei ^{[1
,2
,3
]}

Hu, Chenfei ^{[1
,2
,3
]}

Xu, Qing ^{[1
,2
,3
]}

Chen, Lechuang ^{[1
,2
,3
]}

Ma, Kai ^{[1
,2
,3
]}

Xu, Ningzhi ^{[1
,2
,3
]}

Zhu, Hongxia ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Med Sci, Canc Hosp, Lab Cell & Mol Biol, Beijing 100730, Peoples R China

[2] Chinese Acad Med Sci, Canc Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China

[3] Peking Union Med Coll, Beijing 100021, Peoples R China

来源：

BIOSCIENCE REPORTS | 2015年 / 35卷

关键词：

kelch-like ECH-associated protein 1 (Keap1); Krupple-like factor 4 (KLF4); micro-ribonucleic acid-200a (miR-200a); methylseleninic acid (MSA); nuclear factor E2-related factor 2 (Nrf2); oesophageal squamous cell carcinoma (ESCC); NRF2-KEAP1 SIGNALING PATHWAY; HUMAN PROSTATE-CANCER; OXIDATIVE STRESS; GASTRIC CANCERS; IN-VIVO; CARCINOGENESIS; SELENIUM; NRF2; CHEMOPREVENTION; INHIBITION;

D O I：

10.1042/BSR20150092

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Oesophageal squamous cell carcinoma (ESCC) occurs at a very high rates in certain regions of China. There are increasing evidences demonstrating that selenium could act as a potential anti-oesophageal cancer agent, but the precise mechanisms involved are still not completely understood. Methylseleninic acid (MSA), as a potent second-generation selenium compound, is a promising chemopreventive agent. Previous studies demonstrated that the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2) system plays a critical role in cancer prevention, but little is known about its association with MSA in ESCC cells. In the present study, we observed that MSA treatment significantly down-regulated Keap1, induced nuclear accumulation of Nrf2 and enhance the antioxidant response element (ARE) promoter activity in ESCC cells. MSA could also significantly induce miR-200a expression and inhibit Keap1 directly. Antagomir-200a could attenuate MSA treatment-induced Keap1 down-regulation in ESCC cells. Moreover, MSA-induced miR-200a expression was dependent on the mediation of Krupple-like factor 4 (KLF4). These results reaffirm the potential role of MSA as a chemopreventive agent via the regulation of KLF4/miR-200a/Keap1/Nrf2 axis in ESCC cells.

引用

页数：8

共 30 条

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