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lncRNA HOTAIR upregulates autophagy to promote apoptosis and senescence of nucleus pulposus cells
Author(s) -
Zhan Shengfeng,
Wang Kun,
Xiang Qian,
Song Yu,
Li Shuai,
Liang Hang,
Luo Rongjin,
Wang Bingjin,
Liao Zhiwei,
Zhang Yukun,
Yang Cao
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29129
Subject(s) - hotair , autophagy , microbiology and biotechnology , gene silencing , small interfering rna , ampk , senescence , apoptosis , biology , programmed cell death , chemistry , cancer research , downregulation and upregulation , long non coding rna , protein kinase a , kinase , transfection , cell culture , biochemistry , genetics , gene
Abstract Intervertebral disc degeneration (IDD) is a complex and chronic disease that involves disc cell senescence, death, and extracellular matrix (ECM) degradation. HOTAIR, a long non‐coding RNA (lncRNA) is reportedly associated with autophagy, whereas autophagy is shown to promote IDD. However, how it affects nucleus pulposus (NP) cells, the primary component of intervertebral discs is still unclear. We hypothesized that HOTAIR promotes NP cell apoptosis and senescence through upregulating autophagy. Thus, silencing HOTAIR should inhibit autophagy and exert a therapeutic effect on IDD. Our in vitro experiments in human NP cells revealed that HOTAIR expression positively correlated with IDD grade, and overexpression enhanced autophagy. Autophagy inhibition via 3‐methyladenine reversed HOTAIR stimulatory effects on apoptosis, senescence, and ECM catabolism, while the AMP‐activated protein kinase (AMPK) inhibitor Compound C suppressed HOTAIR‐induced autophagy through regulating AMPK/mTOR/ULK1 pathways. Our in vivo experiment then illustrated that silencing HOTAIR ameliorates IDD in rats. Collectively, we demonstrated that HOTAIR stimulates autophagy to promote NP cell apoptosis, senescence, and ECM catabolism. Therefore, silencing HOTAIR has the potential to become a treatment option for IDD.