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LncRNA H19 targets miR‐22 to modulate H 2 O 2 ‐induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling
Author(s) -
Wang Xiaobin,
Zou Mingxiang,
Li Jing,
Wang Bing,
Zhang Qianshi,
Liu Fubin,
Lü Guohua
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26738
Subject(s) - wnt signaling pathway , senescence , microbiology and biotechnology , cell growth , chemistry , cell , competing endogenous rna , signal transduction , biology , downregulation and upregulation , biochemistry , gene , long non coding rna
Intervertebral disc (IVD) degeneration (IDD) is a major contributor to low back pain. During IDD progression, ROS can be produced in the form of H 2 O 2 in nucleus pulposus cells (NPCs) in response to elevated cytokines, leading to subsequent alternations of cell fate and metabolic processes. Genetic factors are considered as main contributors to IDD pathopoiesis. Herein, we investigated the detailed function and mechanism of H19, one of the most up‐regulated lncRNAs in IDD specimens, in H 2 O 2 ‐induced cell senescence model in NPCs. H19 could accelerate H 2 O 2 ‐induced degenerative changes by promoting cell senescence, increasing ADAMTS‐5 and MMPs protein levels and Collagen I content, as well as suppressing NPC proliferation through activating Wnt/β‐catenin signaling. Moreover, miR‐22, a direct target of H19, could bind to the 3′UTR of LEF1 to inhibit its expression and reverse the effect of H19 on NPCs, thus inhibiting Wnt/β‐catenin signaling. Taken together, H19 acts as a ceRNA to compete with LEF1 for miR‐22, thus modulating downstream Wnt/β‐catenin signaling in NPCs; H19/miR‐22/LEF1 might be a novel target for improving H 2 O 2 ‐induced NPC senescence and treatment for IDD.