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Research Paper|Volume 12, Issue 24|pp 25528—25546

miRNA-122-5p stimulates the proliferation and DNA synthesis and inhibits the early apoptosis of human spermatogonial stem cells by targeting CBL and competing with lncRNA CASC7

Fan Zhou2, Wei Chen1, Yinghong Cui1, Bang Liu1, Qingqing Yuan2, Zheng Li3, Zuping He1,4
  • 1Hunan Normal University School of Medicine, Changsha 410013, Hunan, China
  • 2State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Department of Plastic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
  • 3Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
  • 4The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Changsha 410013, Hunan, China
Received: January 20, 2020Accepted: August 25, 2020Published: November 24, 2020
https://doi.org/10.18632/aging.104158

Copyright: © 2020 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Epigenetic regulators of human spermatogonia stem cells (SSCs) remain largely unknown. We found that miRNA-122-5p was upregulated in human spermatogonia from obstructive azoospermia (OA) patients compared with non-obstructive azoospermia (NOA). MiRNA-122-5p stimulated the proliferation and DNA synthesis of human SSCs, whereas it inhibited the early apoptosis of human SSCs. CBL was predicted and identified as a direct target of miRNA-122-5p in human SSCs. CBL silencing led to an enhancement of cell proliferation and DNA synthesis and neutralized the effect of miRNA-122-5p inhibitor on the DNA synthesis of human SSCs. The decrease in the early apoptosis of human SSCs was observed after CBL knockdown. By comparing the profiles of lncRNAs between OA and NOA spermatogonia, CASC7 was significantly deficient in OA spermatogonia, and it had a direct association with miRNA-122-5p. LncRNA CASC7 competed with miRNA-122-5p, and it suppressed the inhibition of CBL. Collectively, these results implicate that miRNA-122-5p enhances the proliferation and DNA synthesis and inhibits the early apoptosis of human SSCs by targeting CBL and competing with lncRNA CASC7. Therefore, this study provides novel insights into epigenetic regulation of fate determinations of human SSCs, and it offers new targets for gene therapy of male infertility that is associated with aging.