miR-222 induces apoptosis in human intervertebral disc nucleus pulposus cells by targeting Bcl-2

Intervertebral disc degeneration (IDD) is characterized by abnormal induction of apoptosis in intervertebral disc nucleus pulposus (NP) cells. Previous studies indicated that miR-222 was upregulated in patients with rheumatoid arthritis. However, the effects of miR-222 in IDD remain unclear. The present study aimed to demonstrate the role of miR-222 in NP cells. The levels of miR-222 in patients with IDD were measured by reverse transcription-quantitative PCR. Cell Counting Kit-8 and western blotting assays were used to detect cell proliferation and apoptosis-associated protein levels, respectively. In addition, luciferase reporter assays were performed to validate the predicted target genes of miR-222. miR-222 was significantly upregulated in patients with IDD. Overexpression of miR-222 inhibited cell proliferation and induced cell apoptosis. Moreover, overexpression of miR-222 resulted in an upregulation in the levels of Bax and cleaved caspase 3, and a downregulation in the levels of Bcl-2 in NP cells. The luciferase reporter assays demonstrated that Bcl-2 is a target of miR-222. Furthermore, overexpression of miR-222 increased the levels of cytochrome c, apoptotic protease activating factor-1 and cleaved caspase 9 in NP cells. Conversely, downregulation of miR-222 could promote the proliferation of NP cells. The present data demonstrated that miR-222 induced apoptosis in NP cells by directly targeting Bcl-2. Therefore, miR-222 may act as a potential therapeutic target for the treatment of IDD.