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MicroRNA-494 promotes apoptosis and extracellular matrix degradation in degenerative human nucleus pulposus cells.
Oncotarget. 2017 Apr 25; 8(17):27868-27881.O

Abstract

PURPOSE

This study investigated the expression and function of the microRNA-494 in intervertebral disc degeneration (IDD).

RESULTS

MicroRNA-494 expression was upregulated during IDD progression; its overexpression increased the expression of ECM catabolic factors such as matrix metalloproteinase and A disintegrin and metalloproteinase with thrombospondin motif in NP cells while decreasing that of anabolic genes such as type II collagen and aggrecan; it also induced the apoptosis of NP cells, as determined by flow cytometry. These effects were reversed by microRNA-494 inhibitor treatment. SOX9 was identified as a target of negative regulation by microRNA-494. Promoter hypomethylation and NF-κB activation were associated with microRNA-494 upregulation in IDD.

MATERIALS AND METHODS

MicroRNA-494 expression in degenerative nucleus pulposus (NP) tissue was assessed by quantitative real-time PCR. The effect of microRNA-494 on extracellular matrix (ECM) metabolism and NP cell apoptosis was evaluated by transfection of microRNA-494 mimic or inhibitor. The regulation of SRY-related high mobility group box (SOX)9 expression by microRNA-494 was assessed with the luciferase reporter assay, and the methylation status of the microRNA-494 promoter was evaluated by methylation-specific PCR and bisulfite sequencing PCR. The role of activated nuclear factor (NF)-κB in the regulation of microRNA-494 expression was evaluated using specific inhibitors.

CONCLUSIONS

MicroRNA-494 promotes ECM degradation and apoptosis of degenerative human NP cells by directly targeting SOX9.

Authors+Show Affiliations

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, First Hospital of Wuhan, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28427186

Citation

Kang, Liang, et al. "MicroRNA-494 Promotes Apoptosis and Extracellular Matrix Degradation in Degenerative Human Nucleus Pulposus Cells." Oncotarget, vol. 8, no. 17, 2017, pp. 27868-27881.
Kang L, Yang C, Song Y, et al. MicroRNA-494 promotes apoptosis and extracellular matrix degradation in degenerative human nucleus pulposus cells. Oncotarget. 2017;8(17):27868-27881.
Kang, L., Yang, C., Song, Y., Zhao, K., Liu, W., Hua, W., Wang, K., Tu, J., Li, S., Yin, H., & Zhang, Y. (2017). MicroRNA-494 promotes apoptosis and extracellular matrix degradation in degenerative human nucleus pulposus cells. Oncotarget, 8(17), 27868-27881. https://doi.org/10.18632/oncotarget.15838
Kang L, et al. MicroRNA-494 Promotes Apoptosis and Extracellular Matrix Degradation in Degenerative Human Nucleus Pulposus Cells. Oncotarget. 2017 Apr 25;8(17):27868-27881. PubMed PMID: 28427186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-494 promotes apoptosis and extracellular matrix degradation in degenerative human nucleus pulposus cells. AU - Kang,Liang, AU - Yang,Cao, AU - Song,Yu, AU - Zhao,Kangcheng, AU - Liu,Wei, AU - Hua,Wenbin, AU - Wang,Kun, AU - Tu,Ji, AU - Li,Shuai, AU - Yin,Huipeng, AU - Zhang,Yukun, PY - 2016/12/12/received PY - 2017/02/20/accepted PY - 2017/4/22/pubmed PY - 2018/4/4/medline PY - 2017/4/22/entrez KW - SOX9 KW - intervertebral disc degeneration KW - methylation KW - miR-494 KW - nucleus pulposus SP - 27868 EP - 27881 JF - Oncotarget JO - Oncotarget VL - 8 IS - 17 N2 - PURPOSE: This study investigated the expression and function of the microRNA-494 in intervertebral disc degeneration (IDD). RESULTS: MicroRNA-494 expression was upregulated during IDD progression; its overexpression increased the expression of ECM catabolic factors such as matrix metalloproteinase and A disintegrin and metalloproteinase with thrombospondin motif in NP cells while decreasing that of anabolic genes such as type II collagen and aggrecan; it also induced the apoptosis of NP cells, as determined by flow cytometry. These effects were reversed by microRNA-494 inhibitor treatment. SOX9 was identified as a target of negative regulation by microRNA-494. Promoter hypomethylation and NF-κB activation were associated with microRNA-494 upregulation in IDD. MATERIALS AND METHODS: MicroRNA-494 expression in degenerative nucleus pulposus (NP) tissue was assessed by quantitative real-time PCR. The effect of microRNA-494 on extracellular matrix (ECM) metabolism and NP cell apoptosis was evaluated by transfection of microRNA-494 mimic or inhibitor. The regulation of SRY-related high mobility group box (SOX)9 expression by microRNA-494 was assessed with the luciferase reporter assay, and the methylation status of the microRNA-494 promoter was evaluated by methylation-specific PCR and bisulfite sequencing PCR. The role of activated nuclear factor (NF)-κB in the regulation of microRNA-494 expression was evaluated using specific inhibitors. CONCLUSIONS: MicroRNA-494 promotes ECM degradation and apoptosis of degenerative human NP cells by directly targeting SOX9. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/28427186/MicroRNA_494_promotes_apoptosis_and_extracellular_matrix_degradation_in_degenerative_human_nucleus_pulposus_cells_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=15838 DB - PRIME DP - Unbound Medicine ER -