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

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.

Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism

“…In the present study, the level of lncRNA PART1 expression was detected in 10 ng/ml LPS-stimulated NP cells. Previous reports have demonstrated that PART1 expression was upregulated in patients with IDD (17,18). In line with previous studies, the results of the present study indicated that the level of lncRNA PART1 was higher in LPS-stimulated NP cells compared with that in normal untreated cells.…”

“…In particular, lncRNA PART1 is a newly discovered lncRNA that has been previously reported to serve as either an oncogene or suppressor gene in tumors ( 14 , 26 , 37 ). Accumulating studies have suggested that aberrantly expressed lncRNA PART1 is associated with the progression of various diseases, including IDD ( 36 , 17 , 18 ). Lou et al ( 38 ) revealed that lncRNA PART1 promoted the development of colorectal cancer via the miR-150-5p/leucine rich α2-glycoprotein 1 axis.…”

“…lncRNA PART1 has been reported to be upregulated in the central nucleus pulposus tissue of patients with IDD ( 17 ). In addition, a recent study reported that lncRNA PART1 promotes IDD by downregulating the miR-93/MMP2 pathway in nucleus pulposus cells ( 18 ). However, the specific mechanism underlying the role of PART1 in IDD is not completely understood.…”

Construction of a Potentially Functional circRNA-miRNA-mRNA Network in Intervertebral Disc Degeneration by Bioinformatics Analysis

“…MMP2 is known to play a significant role in the process of IDD [ 41 ]. Song et al [ 34 ] found that miR-874-3p protected the intervertebral disc from degeneration by suppressing the expression of MMP2 and MMP3.…”

Diagnostic and Prognostic Significance of miR-675-3p in Patients With Atherosclerosis

“…The thermocycling condition used were as follows: 95°C for 10 min followed by 40 cycles of 94°C for 15 sec, 55°C for 30 sec and 70°C for 30 sec. 20 …”