title: miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling.
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.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. guke11@yeah.net.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. huangxiangwang2015@126.com.
authors.forename: Xiangwang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. aiguke@yeah.net.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. kkllee1@yeah.net.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. yyiiaa1@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. bbjjaa@yeah.net.
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Xiang
authors.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. aayyii1@126.com.
authors.forename: Xiongjie
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. hahaii1@163.com.
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Hunan Provincial People's Hospital, Changsha 10005, China. kakaai@yeah.net.
authors.forename: Bin
authors.initials: B
authors.lastname: Sheng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012600:Scoliosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase