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

Bioscience Reports
Mei LiuHongxia Zhu

Abstract

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 Krüpple-like factor 4 (KLF4). These results reaffirm the potential role of MSA as a chemopreventive agent via the regulation of KLF4/miR-200a/...Continue Reading

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Citations

Jun 5, 2020·Antioxidants·Álvaro García-GuedeInmaculada Ibáñez-de-Caceres
May 18, 2019·Oxidative Medicine and Cellular Longevity·Emiliano Panieri, Luciano Saso
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Jul 9, 2021·Frontiers in Cell and Developmental Biology·Yuan ZhiKeqian Zhi
Jul 30, 2020·Gene·Caroline Izak CuzziolEny Maria Goloni-Bertollo

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Methods Mentioned

BETA
PCR
transfection
immunoprecipitation
ChIP
acetylation

Software Mentioned

Gel
SPSS
- Pro Analyzer

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