The aberrant proliferation of nucleus pulposus (NP) cells has been reported to be implicated in the pathogenesis of intervertebral disc degeneration (IDD). Previous studies have demonstrated that microRNAs (miRNAs), which are a group of small noncoding RNAs, are critical regulators of cell proliferation in various pathologies. However, the role of miRNA-96 (miR-96) in the proliferation of NP cells remains to be determined. In the present study, reverse transcription-quantitative polymerase chain reaction was used to investigate the expression of miR-96 in NP tissues from patients with IDD and healthy tissues from patients with traumatic lumbar fracture as the control. A dual-luciferase reporter assay was used to investigate whether AT-rich interaction domain 2 (ARID2) may be a direct target gene for miR-96. Furthermore, isolated NP cells from patients with IDD were transfected with miR-96 mimics and ARID2-targeting small interfering RNAs; cell proliferation, and the protein expression of Akt, phosphorylated Akt and ARID2 were examined, whereas the effects of an Akt inhibitor on NP cell proliferation were also evaluated. The present results demonstrated that miR-96 expression was significantly upregulated in IDD samples, and the level of miR-96 expression was positively associated with disc degeneration grade, which was evaluated by a modified Pfirrmann grading system. In addition, the current study identified ARID2 as a direct gene target of miR-96. Furthermore, it was demonstrated that ARID2 mRNA expression was inversely correlated with the expression of miR-96 in NP tissues. In addition, miR-96 overexpression promoted NP cell proliferation and induced Akt phosphorylation, which led to increased cyclin D1 translation. Notably, overexpression of ARID2 or treatment with an Akt inhibitor decreased the effect of miR-96 on NP cell proliferation. In conclusion, the results of the present study indicate that miR-96 may promote the proliferation of human degenerated NP cells by targeting ARID2 via activation of the Akt pathway, and potentially serves as a therapeutic target for IDD.
[1]Guilin Med Univ, Dept Orthoped Surg, Affiliated Hosp, 15 Lequn Rd, Guilin 541001, Guangxi, Peoples R China.
[2]Fudan Univ, Shanghai Canc Ctr, Dept Emergency Med, Shanghai 200032, Peoples R China.
[3]Gannan Med Univ, Dept Orthoped Surg, Affiliated Hosp 1, Ganzhou 341000, Jiangxi, Peoples R China.
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