Open Access

MicroRNA‑137 exerts protective effects on hypoxia‑induced cell injury by inhibiting autophagy/mitophagy and maintaining mitochondrial function in breast cancer stem‑like cells

  • Authors:
    • Qiongying Hu
    • Yun Yuan
    • Yeke Wu
    • Yongliang Huang
    • Ziyi Zhao
    • Chong Xiao
  • View Affiliations

  • Published online on: August 3, 2020     https://doi.org/10.3892/or.2020.7714
  • Pages: 1627-1637
  • Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer stem‑like cells (BCSCs) have been identified and proven to play critical roles in tumorigenesis and progression. Hypoxia is a common pathologic feature of breast cancer and potentially, at least in part, regulates the initiation, progression, and recurrence of breast cancer. However, less is known about how hypoxia regulates BCSCs. As several well‑known microRNAs respond to hypoxia, we aimed to determine how hypoxia regulates the physiological processes of BCSCs by regulating the corresponding microRNAs. As expected, microRNA‑137 (miRNA‑137 or miR‑137) was downregulated upon hypoxic exposure, indicating that it may play critical roles in BCSCs. Introduction of miR‑137 mimics promoted cell cycle entry and inhibited hypoxia‑induced cell apoptosis as determined by cell cycle assay and apoptosis assay. By detecting mitochondrial reactive oxygen species (ROS), it was found that miR‑137 inhibited ROS accumulation induced by hypoxic exposure and thus suppressed cell apoptosis. Introduction of miR‑137 mimics under hypoxia inhibited mitophagy/autophagy by targeting FUN14 domain containing 1 (Fundc1) and thus promoted mitochondrial functions, including mitochondrial mass, ATP synthesis and mitochondrial transcriptional activity, which was similar to the effects of Fundc1 knockdown by specific siRNA. Based on these observations, we hypothesized that the survival of BCSCs under hypoxia was mediated by miR‑137 by regulating mitochondrial dysfunction. We demonstrated here that the introduction of exogenous miR‑137 promoted mitochondrial function, indicating that it may be a potential therapeutic target in BCSCs.
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October-2020
Volume 44 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Hu Q, Yuan Y, Wu Y, Huang Y, Zhao Z and Xiao C: MicroRNA‑137 exerts protective effects on hypoxia‑induced cell injury by inhibiting autophagy/mitophagy and maintaining mitochondrial function in breast cancer stem‑like cells. Oncol Rep 44: 1627-1637, 2020
APA
Hu, Q., Yuan, Y., Wu, Y., Huang, Y., Zhao, Z., & Xiao, C. (2020). MicroRNA‑137 exerts protective effects on hypoxia‑induced cell injury by inhibiting autophagy/mitophagy and maintaining mitochondrial function in breast cancer stem‑like cells. Oncology Reports, 44, 1627-1637. https://doi.org/10.3892/or.2020.7714
MLA
Hu, Q., Yuan, Y., Wu, Y., Huang, Y., Zhao, Z., Xiao, C."MicroRNA‑137 exerts protective effects on hypoxia‑induced cell injury by inhibiting autophagy/mitophagy and maintaining mitochondrial function in breast cancer stem‑like cells". Oncology Reports 44.4 (2020): 1627-1637.
Chicago
Hu, Q., Yuan, Y., Wu, Y., Huang, Y., Zhao, Z., Xiao, C."MicroRNA‑137 exerts protective effects on hypoxia‑induced cell injury by inhibiting autophagy/mitophagy and maintaining mitochondrial function in breast cancer stem‑like cells". Oncology Reports 44, no. 4 (2020): 1627-1637. https://doi.org/10.3892/or.2020.7714