lncRNA LINC00284 promotes nucleus pulposus cell proliferation and ECM synthesis via regulation of the miR‑205‑3p/Wnt/β‑catenin axis

Zhu,Min; Yan,Xiaoling; Zhao,Yin; Xue,Huawei; Wang,Zhen; Wu,Bo; Li,Xiangyang; Shen,Yixin

doi:10.3892/mmr.2022.12695

lncRNA LINC00284 promotes nucleus pulposus cell proliferation and ECM synthesis via regulation of the miR‑205‑3p/Wnt/β‑catenin axis

Authors:
- Min Zhu
- Xiaoling Yan
- Yin Zhao
- Huawei Xue
- Zhen Wang
- Bo Wu
- Xiangyang Li
- Yixin Shen
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Affiliations: Department of Spine Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Chemotherapy Department, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Spine Surgery, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China, Department of Spine Surgery, Nantong Third People's Hospital, Nantong, Jiangsu 226006, P.R. China
Published online on: March 22, 2022 https://doi.org/10.3892/mmr.2022.12695
Article Number: 179
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intervertebral disc degeneration (IDD) is a leading cause of degenerative spinal disease. Long non‑coding RNA (lncRNA) LINC00284 is overexpressed in multiple types of cancer and promotes cancer cell proliferation and inhibits apoptosis; however, its role in human IDD and nucleus pulposus (NP) remain unclear. In the present study, intervertebral disc (IVD) tissues were collected from IDD patients for detection of LINC00284 expression using reverse transcription‑quantitative PCR, the binding effect between miR‑205‑3p and LINC00284 was validated by dual‑luciferase reporter assay. miR‑205‑3p and small interfering RNA (siRNA) was used for LINC00240 knockdown to investigate the proliferation, apoptosis of cells in the NP cells measured by Cell Counting Kit (CCK)‑8 assay and Annexin V‑FITC/Propidium Iodide (PI) staining with flow cytometry receptivity. IDD animal models were constructed for in vivo study of the role LINC00284 in IDD improvement. The results showed that LINC00284 expression was upregulated in IDD tissue and IL‑1β‑induced NP cells. LINC00284 knockdown resulted in an increase in IL‑1β‑induced NP cell proliferation, a decrease in apoptosis and matrix metalloproteinase‑3 expression and an increase in expression of extracellular matrix (ECM) markers aggrecan and collagen II. In vivo experiments and histomorphometric analysis confirmed the protective effect of LINC00284 knockdown in IDD. LINC00284 was also shown to be a target of microRNA (miR)‑205‑3p, and there was a negative correlation between LINC00284 and miR‑205‑3p levels in IDD tissue. Additionally, LINC00284 knockdown or miR‑205‑3p upregulation resulted in inhibition of Wnt/β‑catenin signaling and subsequent degradation of the ECM. The present study demonstrated that LINC00284 activated the Wnt/β‑catenin signaling via sponging miR‑205‑3p, resulting in inhibition of NP cell proliferation and ECM synthesis. These results suggested that targeting LINC00284 to rescue miR‑205‑3p expression may be a potential method for IDD management.

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