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miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling.
Int J Mol Sci. 2014 Mar 05; 15(3):4007-18.IJ

Abstract

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.

Authors+Show Affiliations

Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. guke11@yeah.net.Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. huangxiangwang2015@126.com.Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. aiguke@yeah.net.Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. kkllee1@yeah.net.Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. yyiiaa1@163.com.Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. bbjjaa@yeah.net.Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. aayyii1@126.com.Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. hahaii1@163.com.Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. kakaai@yeah.net.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24603539

Citation

Liu, Hongzhe, et al. "MiR-21 Promotes Human Nucleus Pulposus Cell Proliferation Through PTEN/AKT Signaling." International Journal of Molecular Sciences, vol. 15, no. 3, 2014, pp. 4007-18.
Liu H, Huang X, Liu X, et al. MiR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. Int J Mol Sci. 2014;15(3):4007-18.
Liu, H., Huang, X., Liu, X., Xiao, S., Zhang, Y., Xiang, T., Shen, X., Wang, G., & Sheng, B. (2014). MiR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. International Journal of Molecular Sciences, 15(3), 4007-18. https://doi.org/10.3390/ijms15034007
Liu H, et al. MiR-21 Promotes Human Nucleus Pulposus Cell Proliferation Through PTEN/AKT Signaling. Int J Mol Sci. 2014 Mar 5;15(3):4007-18. PubMed PMID: 24603539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. AU - Liu,Hongzhe, AU - Huang,Xiangwang, AU - Liu,Xiangyang, AU - Xiao,Sheng, AU - Zhang,Yi, AU - Xiang,Tiecheng, AU - Shen,Xiongjie, AU - Wang,Guoping, AU - Sheng,Bin, Y1 - 2014/03/05/ PY - 2013/11/24/received PY - 2014/01/16/revised PY - 2014/01/26/accepted PY - 2014/3/8/entrez PY - 2014/3/8/pubmed PY - 2015/2/14/medline SP - 4007 EP - 18 JF - International journal of molecular sciences JO - Int J Mol Sci VL - 15 IS - 3 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/24603539/miR_21_promotes_human_nucleus_pulposus_cell_proliferation_through_PTEN/AKT_signaling_ L2 - http://www.mdpi.com/resolver?pii=ijms15034007 DB - PRIME DP - Unbound Medicine ER -