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LncRNA H19 targets miR-22 to modulate H2 O2 -induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling

TitleLncRNA H19 targets miR-22 to modulate H2 O2 -induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling
Publication TypeJournal Article
Year of Publication2018
AuthorsWang, X, Zou, M, Li, J, Wang, B, Zhang, Q, Liu, F, Lu, G
JournalJ Cell Biochem
Volume119
Pagination4990-5002
Date PublishedJun
ISBN Number0730-2312
Accession Number29520849
Keywordscell senescence, H19, miR-22, nucleus pulposus cell (NPC), reactive oxygen species (ROS), Wnt/beta-catenin signaling
Abstract

Intervertebral disc (IVD) degeneration (IDD) is a major contributor to low back pain. During IDD progression, ROS can be produced in the form of H2 O2 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 H2 O2 -induced cell senescence model in NPCs. H19 could accelerate H2 O2 -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/beta-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/beta-catenin signaling. Taken together, H19 acts as a ceRNA to compete with LEF1 for miR-22, thus modulating downstream Wnt/beta-catenin signaling in NPCs; H19/miR-22/LEF1 might be a novel target for improving H2 O2 -induced NPC senescence and treatment for IDD.