Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the miR‑93/MMP2 pathway in nucleus pulposus cells

Gao,Dongmei; Hao,Long; Zhao,Zilong

doi:10.3892/ijmm.2020.4580

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the miR‑93/MMP2 pathway in nucleus pulposus cells

Authors:
- Dongmei Gao
- Long Hao
- Zilong Zhao
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Affiliations: Department of Pain Rehabilitation, Yan'an University Affiliated Hospital, Yan'an, Shaanxi 716000, P.R. China, Department of Pathology, Ankang Central Hospital, Ankang, Shaanxi 725000, P.R. China
Published online on: April 16, 2020 https://doi.org/10.3892/ijmm.2020.4580
Pages: 289-299
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the role of the long non‑coding (lnc)RNA PART1 in nucleus pulposus (NP) cells derived from patients with intervertebral disc degeneration (IDD). The level of PART1 in degenerative NP tissues from patients with IDD, bulging and herniated discs was measured by reverse transcription‑quantitative PCR (RT‑qPCR) analysis. NP cells were isolated from patients with IDD and transfected with siPART1, after which time the growth ability of the NP cells was evaluated by Cell Counting Kit‑8 and colony formation assays, and cell apoptosis was measured by flow cytometry. The levels of the cell proliferation marker Ki‑67 and the apoptosis marker cleaved caspase‑3, and the levels of genes related to extracellular matrix (ECM) synthesis and degradation, were also evaluated by western blotting and RT‑qPCR, as appropriate. Bioinformatics methods predicted that miR‑93 was sponged by PART1, and matrix metallopeptidase (MMP)2 was targeted by miR‑93, which was further confirmed by dual‑luciferase reporter assay. The levels of miR‑93 and MMP2 were also measured in NP tissues, and further rescue experiments were performed to confirm the role of the PART1/miR‑93/MMP2 pathway in NP cells. PART1 was found to be upregulated in degenerative NP tissues, and siPART1 caused an increase in cell growth ability and ECM synthesis, whereas it decreased cell apoptosis and ECM degradation in NP cells. miR‑93 was downregulated and MMP2 was upregulated in degenerative NP tissues. Rescue experiments indicated that the effects of miR‑93 inhibitor on NP cells were abolished by siPART1, and the effect of miR‑93 mimic on NP cells was rescued by MMP2 overexpression. Thus, the results of the present study demonstrated that PART1 may regulate NP cell degeneration through the miR‑93/MMP2 pathway. These findings indicate a novel signaling axis in NP cells that may be explored for the treatment of IDD.

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