Open Access

miR‑125b‑5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS‑induced intestinal mucosa cell injury model

  • Authors:
    • Huiming Guo
    • Jianyuan Gao
    • Yuan Qian
    • Huawei Wang
    • Jiang  Liu
    • Qingyan Peng
    • Yong Zhou
    • Kunhua Wang
  • View Affiliations

  • Published online on: June 6, 2021     https://doi.org/10.3892/etm.2021.10270
  • Article Number: 838
  • Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intestinal barrier injury is an important cause of death in patients with acquired immune deficiency syndrome (AIDS). Therefore, it is of great significance to identify a therapeutic target for intestinal barrier injury to delay the progression of AIDS. microRNA (miRNA/miR)‑125b‑5p has an extensive role in cancer and controlling intestinal epithelial barrier function, but its role in human immunodeficiency virus‑related intestinal mucosal damage remains unknown. The present study was designed to explore the effects of miR‑125b‑5p on lipopolysaccharide (LPS)‑induced intestinal mucosal injury and the underlying mechanism. The expression of miR‑125b‑5p and ASCT2 mRNA was detected in colon biopsy samples of 10 patients with AIDS and 10 control healthy subjects. Human intestinal embryonic mucosa cells (CCC‑HIE‑2) were used to establish an LPS‑induced intestinal mucosa cell injury model in vitro. Cell proliferation and apoptosis were determined by MTT assays and flow cytometry, respectively. miR‑125b‑5p levels and ASCT2 mRNA and protein expression levels in the LPS‑induced intestinal mucosa cell injury model were detected by reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. The interaction between miR‑125b‑5p and ASCT2 was analyzed using a dual luciferase reporter assay. The results demonstrated that miR‑125b‑5p levels were increased and ASCT2 mRNA expression levels were decreased in colon samples from patients with AIDS and in LPS‑induced intestinal mucosa cells. In the LPS‑induced intestinal mucosa cell injury model, transfection with miR‑125b‑5p mimic inhibited cell proliferation and promoted cell apoptosis, while transfection with a miR‑125b‑5p inhibitor increased cell proliferation and attenuated cell apoptosis. Furthermore, miR‑125b‑5p mimic transfection resulted in a decrease of ASCT2 mRNA and protein expression, whereas the inhibitor increased ASCT2 mRNA and protein expression. Dual luciferase reporter assays suggested that ASCT2 was a direct target of miR‑125b‑5p, and its restoration weakened the effect of miR‑125b‑5p on LPS‑induced intestinal mucosa cell injury. Transfection with the miR‑125b‑5p mimic also exhibited a suppressive effect on the PI3K/AKT/mTOR pathway in the LPS‑induced intestinal mucosal cell injury model. Overall, the present study indicated that miR‑125b‑5p accelerated LPS‑induced intestinal mucosa cell injury by targeting ASCT2 and upregulating the PI3K/AKT/mTOR pathway. The current findings may provide novel targets for the treatment of intestinal barrier injury in patients with AIDS.
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August-2021
Volume 22 Issue 2

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Spandidos Publications style
Guo H, Gao J, Qian Y, Wang H, Liu J, Peng Q, Zhou Y and Wang K: miR‑125b‑5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS‑induced intestinal mucosa cell injury model. Exp Ther Med 22: 838, 2021
APA
Guo, H., Gao, J., Qian, Y., Wang, H., Liu, J., Peng, Q. ... Wang, K. (2021). miR‑125b‑5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS‑induced intestinal mucosa cell injury model. Experimental and Therapeutic Medicine, 22, 838. https://doi.org/10.3892/etm.2021.10270
MLA
Guo, H., Gao, J., Qian, Y., Wang, H., Liu, J., Peng, Q., Zhou, Y., Wang, K."miR‑125b‑5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS‑induced intestinal mucosa cell injury model". Experimental and Therapeutic Medicine 22.2 (2021): 838.
Chicago
Guo, H., Gao, J., Qian, Y., Wang, H., Liu, J., Peng, Q., Zhou, Y., Wang, K."miR‑125b‑5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS‑induced intestinal mucosa cell injury model". Experimental and Therapeutic Medicine 22, no. 2 (2021): 838. https://doi.org/10.3892/etm.2021.10270