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MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration.
PLoS One. 2013; 8(12):e83080.Plos

Abstract

Aberrant proliferation of nucleus pulposus cell is implicated in the pathogenesis of intervertebral disc degeneration. Recent findings revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many pathological conditions. Here, we showed that miR-10b was dramatically upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues isolated from patients with idiopathic scoliosis. Moreover, miR-10b levels were associated with disc degeneration grade and downregulation of HOXD10. In cultured nucleus pulposus cells, miR-10b overexpression stimulated cell proliferation with concomitant translational inhibition of HOXD10 whereas restored expression of HOXD10 reversed the mitogenic effect of miR-10b. MiR-10b-mediated downregulation of HOXD10 led to increased RhoC expression and Akt phosphorylation. Either knockdown of RhoC or inhibition of Akt abolished the effect of miR-10b on nucleus pulposus cell proliferation. Taken together, aberrant miR-10b upregulation in intervertebral disc degeneration could contribute to abnormal nucleus pulposus cell proliferation through derepressing the RhoC-Akt pathway by targeting HOXD10. Our study also underscores the potential of miR-10b and the RhoC-Akt pathway as novel therapeutic targets in intervertebral disc degeneration.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China ; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road, Xicheng District, Beijing, China.Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.Institute of Digestive Disease and State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences & Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24376640

Citation

Yu, Xin, et al. "MicroRNA-10b Promotes Nucleus Pulposus Cell Proliferation Through RhoC-Akt Pathway By Targeting HOXD10 in Intervetebral Disc Degeneration." PloS One, vol. 8, no. 12, 2013, pp. e83080.
Yu X, Li Z, Shen J, et al. MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PLoS ONE. 2013;8(12):e83080.
Yu, X., Li, Z., Shen, J., Wu, W. K., Liang, J., Weng, X., & Qiu, G. (2013). MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PloS One, 8(12), e83080. https://doi.org/10.1371/journal.pone.0083080
Yu X, et al. MicroRNA-10b Promotes Nucleus Pulposus Cell Proliferation Through RhoC-Akt Pathway By Targeting HOXD10 in Intervetebral Disc Degeneration. PLoS ONE. 2013;8(12):e83080. PubMed PMID: 24376640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. AU - Yu,Xin, AU - Li,Zheng, AU - Shen,Jianxiong, AU - Wu,William K K, AU - Liang,Jinqian, AU - Weng,Xisheng, AU - Qiu,Guixing, Y1 - 2013/12/20/ PY - 2013/08/26/received PY - 2013/11/06/accepted PY - 2013/12/31/entrez PY - 2014/1/1/pubmed PY - 2014/10/7/medline SP - e83080 EP - e83080 JF - PloS one JO - PLoS ONE VL - 8 IS - 12 N2 - Aberrant proliferation of nucleus pulposus cell is implicated in the pathogenesis of intervertebral disc degeneration. Recent findings revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many pathological conditions. Here, we showed that miR-10b was dramatically upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues isolated from patients with idiopathic scoliosis. Moreover, miR-10b levels were associated with disc degeneration grade and downregulation of HOXD10. In cultured nucleus pulposus cells, miR-10b overexpression stimulated cell proliferation with concomitant translational inhibition of HOXD10 whereas restored expression of HOXD10 reversed the mitogenic effect of miR-10b. MiR-10b-mediated downregulation of HOXD10 led to increased RhoC expression and Akt phosphorylation. Either knockdown of RhoC or inhibition of Akt abolished the effect of miR-10b on nucleus pulposus cell proliferation. Taken together, aberrant miR-10b upregulation in intervertebral disc degeneration could contribute to abnormal nucleus pulposus cell proliferation through derepressing the RhoC-Akt pathway by targeting HOXD10. Our study also underscores the potential of miR-10b and the RhoC-Akt pathway as novel therapeutic targets in intervertebral disc degeneration. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24376640/MicroRNA_10b_promotes_nucleus_pulposus_cell_proliferation_through_RhoC_Akt_pathway_by_targeting_HOXD10_in_intervetebral_disc_degeneration_ L2 - http://dx.plos.org/10.1371/journal.pone.0083080 DB - PRIME DP - Unbound Medicine ER -