Journal
BIOSCIENCE REPORTS
Volume 35, Issue -, Pages -Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BSR20150092
Keywords
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)
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Funding
- National Natural Science Foundation [81472561, 81321091, 81302279, 81071713, 81021061]
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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.
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