miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling

International Journal of Molecular Sciences

Hongzhe Liu²  Xiangwang Huang¹  Xiangyang Liu²  Sheng Xiao²  Yi Zhang²  Tiecheng Xiang²  Xiongjie Shen²  Guoping Wang² 

[1] Department of Orthopedic Surgery, Hunan Provincial People’s Hospital, Changsha 10005, China;

关键词: disc degeneration;    nucleus pulposus cells;    miRNA;    miR-21;    proliferation;   

DOI  :  10.3390/ijms15034007

来源: mdpi

【 摘 要 】

The precise role of nucleus pulposus cell proliferation in the pathogenesis of intervertebral disc degeneration remains to be elucidated. Recent findings have revealed that microRNAs, a class of small noncoding RNAs, may regulate cell proliferation in many pathological conditions. Here, we showed that miR-21 was significantly upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues that were isolated from patients with idiopathic scoliosis and that miR-10b levels were associated with disc degeneration grade. Moreover, bioinformatics target prediction identified PTEN as a putative target of miR-21. miR-21 inhibited PTEN expression by directly targeting the 3′UTR, and this inhibition was abolished through miR-21 binding site mutations. miR-21 overexpression stimulated cell proliferation and AKT signaling pathway activation, which led to cyclin D1 translation. Additionally, the increase in proliferation and cyclin D1 expression induced by miR-21 overexpression was almost completely blocked by Ly294002, an AKT inhibitor. Taken together, aberrant miR-21 upregulation in intervertebral disc degeneration could target PTEN, which would contribute to abnormal nucleus pulposus cell proliferation through derepressing the Akt pathway. Our study also underscores the potential of miR-21 and the PTEN/Akt pathway as novel therapeutic targets in intervertebral disc degeneration.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland