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LINC01121 induced intervertebral disc degeneration via modulating miR‐150‐5p/MMP16 axis
Author(s) -
Chen Xin,
Li Zheng,
Xu Derong,
Li Shugang
Publication year - 2020
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3231
Subject(s) - matrix metalloproteinase , ectopic expression , intervertebral disc , chemistry , luciferase , cell growth , tumor necrosis factor alpha , cell , microbiology and biotechnology , microrna , cancer research , biology , transfection , immunology , anatomy , gene , biochemistry
Abstract Background Growing evidence indicates that Long noncoding RNAs contribute to cell differentiation, invasion, metabolism, proliferation and metastasis. However, the potential role of LINC01121 in progression of intervertebral disc degeneration (IDD) remains unclear. Methods LINC01121, matrix metalloprotease (MMP)‐16 and miR‐150‐5p expression was determined by a quantitative‐reverse transcriptase‐polymerase chain reaction assay. Inflammatory cytokines level was measured by an enzyme‐linked immunosorbent assay and cell counting kit‐8 analysis was used to assess cell proliferation. MMP‐16‐specific binding with miR‐150‐5p was verified with a luciferase reporter assay. Results We noted that interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α treatment enhanced LINC01121 and MMP‐16 expression in nucleus pulposus (NP) cells. LINC01121 was higher in IDD specimens compared to that in control specimens. Higher expression of LINC01121 was correlated with disc degeneration degree. Ectopic expression of LINC01121 enhanced cell proliferation and promoted ki‐67, MMP‐3 and ADAMTS5 expression and also suppressed collagen II expression in NP cells. We observed that overexpression of LINC01121 increased the secretion of three inflammatory cytokines, including IL‐6, TNF‐α and IL‐1β. We found that ectopic expression of LINC01121 decreased the miR‐150‐5p level in NP cells. Luciferase reporter data confirmed that MMP‐16 was one direct target of miR‐150‐5p. Overexpression of miR‐150‐5p inhibited MMP‐16 level and elevated the expression of LINC01121 enhanced MMP‐16 level. We also found that MMP‐16 was up‐regulated in IDD specimens compared to that in control specimens. Higher expression of MMP‐16 was correlated with disc degeneration degree. Interestingly, MMP‐16 expression was positively related to LINC01121 in IDD specimens. Finally, overexpression of LINC01121 regulated cell growth, extracellular matrix degradation and inflammatory cytokine secretion via modulating MMP‐16. Conclusions our data suggested LINC01121 may be a new therapeutic target for IDD.