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.

<p>Knockdown of hsa_circ_0059955 Induces Apoptosis and Cell Cycle Arrest in Nucleus Pulposus Cells via Inhibiting <em>Itchy E3 Ubiquitin Protein Ligase</em></p>

“…IVDD is characterized by decreased cell proliferation and increased cell death. 28 In this study, downregulation of hsa_circ_0059955 significantly inhibited proliferation, and induced apoptosis of NP cells. These data indicated that decreased expression of hsa_circ_0059955 may contribute to IVDD progression.…”

Treatment of Intervertebral Disc Degeneration

“…There are a variety of molecular mechanisms and biological effects of ncRNAs in regulating IDD (Table S1). 83–171 NcRNAs plays a vital role in cell proliferation, cell apoptosis, cell autophagy, ECM degeneration or degradation, inflammation, and so on. Bcl‐2 is a protein related to the regulation of cell apoptosis, and the apoptosis of NPCs is an important link in IDD, so Bcl‐2 is also an important target in IDD.…”

“…Bcl‐2 is a protein related to the regulation of cell apoptosis, and the apoptosis of NPCs is an important link in IDD, so Bcl‐2 is also an important target in IDD. miRNA‐143, 83 miRNA‐155, 84 and miRNA‐222 85 have been reported to regulate the apoptosis of NPCs by targeting Bcl‐2. lncRNA‐GAS5 acts as a miRNA‐155 sponge to regulate its expression 84 .…”

The Mechanism and Function of miRNA in Intervertebral Disc Degeneration

“…And they delivered the up or down-regulated miR-141 through nanoparticles in the IDD rat model to aggravate or reduce experimental IDD. MiR-22215 was significantly up-regulated in degenerative NPCs. And the overexpressed miR-222 can activate Bax and caspase 3 but inhibit Bcl-2.…”