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ERO1α mediates endoplasmic reticulum stress-induced apoptosis via microRNA-101/EZH2 axis in colon cancer RKO and HT-29 cells

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Abstract

Although colon cancer is a leading and typical gastrointestinal tumor, there is little published data on the underlying molecular mechanisms of endoplasmic reticulum (ER) stress. Here, we investigated the role of ERO1α and its impact on microRNA (miR)-101 expression and ER stress in colon cancer cells. Cell ER stress was established by treating RKO or HT-29 cells with 1 μM thapsigargin (THG). Cell biological behaviors were detected using CCK-8, bromodeoxyuridine assay, flow cytometry and western blot. We also investigated the expression of ERO1α and miR-101 after THG treatment using RT-qPCR. Moreover, effects of ERO1α and miR-101 on ER stress of colon cancer cells were detected. Additionally, miR-101 impact on EZH2 expression and relevance of this regulation was confirmed by RT-qPCR and luciferase reporter. The regulation of miR-101/EZH2 axis and Wnt/β-catenin pathway in ER stress were investigated. Our results demonstrated that THG induced ER stress in colon cancer cells. Silencing ERO1α further promoted ER stress-induced cell apoptosis. ERO1α knockdown up-regulated miR-101 expression and promoted colon cancer cell apoptosis via regulating miR-101. Surprisingly, miR-101 negatively regulated EZH2 expression via miRNA-mRNA targeting. Moreover, ER stress promoted colon cancer cell apoptosis via regulating miR-101/EZH2 axis. Wnt/β-catenin pathway was also involved in the regulation of ERO1α/miR-101/EZH2 in ER stress of colon cancer cells. These findings illustrated that silencing ERO1α regulated ER stress-induced apoptosis via miR-101/EZH2 axis in RKO and HT-29 cells.

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Author notes

  1. Guoqin Wang and Jiangqiong Han are co-first authors.

Authors and Affiliations

  1. Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, Yunnan, China

    Guoqin Wang & Gaowei Wang

  2. Integrated Traditional Chinese and Western Medicine Department, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, Yunnan, China

    Jiangqiong Han

  3. Department Gastrointestinal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China

    Xuesong Wu

  4. Tumor Institute of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China

    Youguang Huang & Min Wu

  5. Cadre Medical Department, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, No. 517 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan, China

    Yunlan Chen

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  1. Guoqin Wang
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Wang, G., Han, J., Wang, G. et al. ERO1α mediates endoplasmic reticulum stress-induced apoptosis via microRNA-101/EZH2 axis in colon cancer RKO and HT-29 cells. Human Cell 34, 932–944 (2021). https://doi.org/10.1007/s13577-021-00494-3

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