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Research Paper Volume 13, Issue 18 pp 22459—22473
miR-19b-3p relieves intervertebral disc degeneration through modulating PTEN/PI3K/Akt/mTOR signaling pathway
- 1 Department of Spine Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, ShanDong University, Qingdao 266035, ShanDong, China
Received: December 27, 2020 Accepted: September 3, 2021 Published: September 23, 2021
https://doi.org/10.18632/aging.203553How to Cite
Copyright: © 2021 Zhao and Li. 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
Emerging studies have revealed that non-coding RNAs contribute to regulating intervertebral disc degeneration (IVDD). Here, we intended to probe into the function of miR-19b-3p in IVDD evolvement. The miR-19b-3p level in the intervertebral disc (IVD) tissues of IVDD patients and IL-1β/TNF-α/hydrogen peroxide-treated human nucleus pulposus cells (HNPCs) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Also, qRT-PCR was conducted to examine the profiles of MMP-3, MMP-9, MMP-13, ADAMTS-4 and ADAMTS-5. The PTEN/PI3K/Akt/mTOR pathway was examined by Western blot (WB). The miR-19b-3p overexpression assay was carried out, and HNPC proliferation and apoptosis were compared by the cell counting kit-8 (CCK-8) assay and flow cytometry (FCM). In addition, the mechanism of action of miR-19b-3p was clarified using the PTEN inhibitor (VO-Ohpic triphosphate) or the mTOR inhibitor (Rapamycin) on the basis of IL-1β intervention and miR-19b-3p mimics transfection. Our results testified that miR-19b-3p expression was curbed in IVD tissues of the IVDD patients (vs. normal IVD tissues) and IL-1β-, TNF-α, or hydrogen peroxide-treated HNPCs. Up-regulating miR-19b-3p enhanced HNPC proliferation and hampered its apoptosis. Moreover, miR-19b-3p dampened the PTEN profile and activated the PI3K/Akt/mTOR pathway. Interestingly, attenuating PTEN reduced IL-1β-, TNF-α-, or hydrogen peroxide-mediated HNPC apoptosis and up-regulated PI3K/Akt/mTOR, while inhibiting the mTOR pathway offset the protective function of miR-19b-3p. Further mechanism studies illustrated that miR-19b-3p targeted the 3’untranslated region (UTR) of PTEN and abated the PTEN level. This research confirmed that miR-19b-3p suppressed HNPC apoptosis in the in-vitro model of IVDD by regulating PTEN/PI3K/Akt/mTOR pathway.