LINC00641 regulates autophagy and intervertebral disc degeneration by acting as a competitive endogenous RNA of miR-153-3p under nutrition deprivation stress.

Emerging evidence supports the involvement of autophagy in the pathogenesis of intervertebral disc degeneration (IDD). MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play fundamental roles in various cellular processes, including autophagy. However, it remains largely unknown as to how autophagy is regulated by miRNAs and lncRNAs in IDD. Biological functions of miR-153-3p and long intergenic nonprotein coding RNA 641 (LINC00641) were investigated. Luciferase reporter assays was done to validate miR-153-3p targets. To induce nutritional stress, nucleus pulposus (NP) cells were cultured in the normal nutritional condition and the low nutritional condition. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to analyze miR-153-3p and LINC00641 in response to nutrient deprivation. Autophagic activity was assessed by transmission electron microscopy, western blot analysis and green fluorescent protein-light chain 3 puncta. Pull-down assay and RNA fluorescent in situ hybridization were performed to validate LINC00641 target and the location. MiR-153-3p is downregulated in NP tissues from IDD patients. Further, LINC00641 can affect collagen II and matrix metalloproteinase-3 expressions. Upregulation of LINC00641 and downregulation of miR-153-3p are detected in NP cells under nutritional stress. LINC00641 can regulate autophagic cell death by targeting miR-153-3p and autophagy-related gene 5 (ATG5). MiR-153-3p inhibits autophagy and IDD by targeting ATG5. More important, LINC00641 targets miR-153-3p, and thus affects ATG5 expression, autophagic cell death and IDD. These findings uncover a novel regulatory pathway that is composed of LINC00641, miR-153-3p, and ATG5 in IDD. This mechanism may stimulate to a more understanding of IDD pathogenesis and provide new sights for the treatment of this disorder.

Wang XB ，Wang H ，Long HQ ，Li DY ，Zheng X ... -  《-》

LncRNA OIP5-AS1 accelerates intervertebral disc degeneration by targeting miR-25-3p.

Che Z ，Xueqin J ，Zhang Z 《-》

microRNA-155-3p attenuates intervertebral disc degeneration via inhibition of KDM3A and HIF1α.

Zhou X ，Li J ，Teng J ，Liu Y ，Zhang D ，Liu L ，Zhang W ... -  《-》

LncRNA H19 Aggravates Intervertebral Disc Degeneration by Promoting the Autophagy and Apoptosis of Nucleus Pulposus Cells Through the miR-139/CXCR4/NF-κB Axis.

Sun Z ，Tang X ，Wang H ，Sun H ，Chu P ，Sun L ，Tian J ... -  《-》

MicroRNA-7 regulates IL-1β-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells.

The precise role of interleukin-1 beta (IL-1β)-induced extracellular matrix degeneration in the pathogenesis of intervertebral disc degeneration (IDD) is currently unknown. Recent evidence has revealed that microRNAs (miRNAs) are associated with IDD, but their function in the extracellular matrix degradation of nucleus pulposus (NP) tissues is also poorly understood. The aim of this study was to evaluate the expression and functional role of miR-7 in IL-1β-induced disc degeneration. The expression level of miR-7 was investigated in degenerative NP tissues and in IL-1β-induced NP cells using quantitative reverse transcription-polymerase chain reaction amplification analysis. A dual-luciferase reporter assay was then utilized to determine whether growth differentiation factor 5 (GDF5) is a target of miR-7. Finally, mRNA and protein levels of known matrix components and of matrix degradation enzymes were determined to elucidate the function of miR-7 in IL-1β-induced disc degeneration. In this study, we found that miR-7 is highly expressed in human degenerative NP tissues and in IL-1β stimulated NP cells compared to normal controls. We also determined that GDF5 was a target of miR-7. Functional analysis showed that the overexpression of miR-7 significantly enhanced the IL-1β-induced extracellular matrix degeneration, whereas inhibition of miR-7 function by antagomiR-7 prevented NP cell detrimental catabolic changes in response to IL-1β. Additionally, the prevention of IL-1β-induced NP extracellular matrix degeneration by miR-7 silencing was attenuated by GDF5 siRNA. These findings suggest that miR-7 contributes to an impaired ECM in intervertebral discs through targeting GDF5 and miR-7 might therefore represent a novel therapeutic target for the prevention of IDD.

Liu W ，Zhang Y ，Xia P ，Li S ，Feng X ，Gao Y ，Wang K ，Song Y ，Duan Z ，Yang S ，Shao Z ，Yang C ... -  《-》