MicroRNA-10b Promotes Nucleus Pulposus Cell Proliferation through RhoC-Akt Pathway by Targeting HOXD10 in Intervetebral Disc Degeneration

• Published in: PloS one Vol. 8; no. 12; p. e83080
• Main Authors: Yu, Xin, Li, Zheng, Shen, Jianxiong, Wu, William K. K., Liang, Jinqian, Weng, Xisheng, Qiu, Guixing
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.12.2013; Public Library of Science (PLoS)
• Subjects: Aberration; Adult; AKT protein; Apoptosis; Cell growth; Cell Proliferation; Chondrocytes - metabolism; Chondrocytes - pathology; Comparative analysis; Degeneration; Development and progression; Disease; Female; Gastric cancer; Gene Expression Regulation; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Hospitals; Humans; Inhibition; Intervertebral Disc Degeneration - genetics; Intervertebral Disc Degeneration - metabolism; Intervertebral Disc Degeneration - pathology; Intervertebral discs; Laboratories; Male; Medical prognosis; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Nuclei; Nuclei (cytology); Nucleus pulposus; Ovarian cancer; Pathogenesis; Phosphorylation; Physiological aspects; Primary Cell Culture; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; rho GTP-Binding Proteins - antagonists & inhibitors; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; rhoC GTP-Binding Protein; Ribonucleic acid; RNA; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Rodents; Scoliosis; Signal Transduction; Spine - metabolism; Spine - pathology; Stomach cancer; Surgery; Tissues; Transcription Factors - genetics; Transcription Factors - metabolism; Beijing China; China
• DOI: 10.1371/journal.pone.0083080
• ISSN: 1932-6203

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.