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LncRNA-RP11-296A18.3/miR-138/HIF1A Pathway Regulates the Proliferation ECM Synthesis of Human Nucleus Pulposus Cells (HNPCs)

TitleLncRNA-RP11-296A18.3/miR-138/HIF1A Pathway Regulates the Proliferation ECM Synthesis of Human Nucleus Pulposus Cells (HNPCs)
Publication TypeJournal Article
Year of Publication2017
AuthorsWang, X, Lv, G, Li, J, Wang, B, Zhang, Q, Lu, C
JournalJ Cell Biochem
Date PublishedDec
ISBN Number0730-2312
Accession Number28543639
Keywords*Cell Proliferation, *Human nucleus pulposus cell (hnpc), *Hypoxia-inducible factor 1-alpha (hif1a), *Intervertebral disc degeneration (idd), *LONG NON-CODING RNA (lncRNA) RP11-296A18.3, *miR-138, Cells, Cultured, Collagen Type I/metabolism, Extracellular Matrix/metabolism, Humans, Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism, Intervertebral Disc/*metabolism, Matrix Metalloproteinase 13/metabolism, MicroRNAs/*metabolism, RNA, Long Noncoding/*metabolism

During the process of Intervertebral disc degeneration (IDD), nucleus pulposus apoptosis increases, extracellular matrix (ECM) alters and/or degrades, abnormal proliferation of cells forms cell clusters, and the expression of various inflammatory factors increases. Thus, regulation of human nucleus pulposus cell (HNPC) proliferation and ECM synthesis present promising strategies for IDD treatment. Accumulating evidence indicates that non-coding RNAs are involved in various cellular processes, including cell proliferation, differentiation, apoptosis, and metastasis. High expression of long non-coding RNA (lncRNA) RP11-296A18.3, as well as a low expression of miR-138 during the IDD process has been reported; yet their functional roles in HNPC proliferation and ECM synthesis still remain unclear. MTT and BrdU assays showed that knockdown of RP11-296A18.3 inhibited the proliferation of HNPC. The ECM marker, MMP-13 and Collagen I expressions were also reduced. Bioinformatics target prediction, qPCR, and luciferase assays identified LncRNA-RP11-296A18.3 interacted with miR-138. Moreover, RP11-296A18.3 regulates HNPC proliferation and ECM synthesis through miR-138. As the target gene of miR-138, hypoxia-inducible factor 1-alpha (HIF1A) was closely associated with cell proliferation which was also regulated by RP11-296A18.3 via miR-138. Immunochemistry and qPCR results showed that miR-138 expression was inversely correlated to RP11-296A18.3 and HIF1A in IDD tissues, respectively; RP11-296A18.3 was positively correlated to HIF1A. We revealed that RP11-296A18.3 promote HIF1A expression through sponging miR-138, thus to promote HNPC proliferation and ECM synthesis. Targeting RP11-296A18.3 to rescue miR-138 expression in HNPCs and IDD tissues presents a promising strategy for IDD improvement. J. Cell. Biochem. 118: 4862-4871, 2017. (c) 2017 Wiley Periodicals, Inc.