MiR‑222 induces apoptosis in human intervertebral disc nucleus pulposus cells by targeting Bcl‑2.

Abstract

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.