January - March 2023, Volume 19, Issue 1

Zhang C, Liu Q, Yin Q

HSA-MIR-183-3P Targeting Ataxia-Telangiectasia Mutated Protein Regulation of NF-KB Signaling Pathway Affects Cellular Senescence Caused by DNA Damage in Lumbar Disc Degeneration

Acta Endo (Buc) 2023, 19 (1): 10-18
doi: 10.4183/aeb.2023.10

Aims. To test the effect of Hsa-miR-183-3p on cell aging and disc degeneration in lumbar intervertebral disc. Methods. This study combined clinical research with basic cell experiment, analyzing clinical data from patients with lumbar disc degeneration and traumatic lumbar spine fracture, as well as the differences in baseline data. The degree of lumbar disc injury in patients of different ages was also compared. Differentially expressed miRNAs were predicted via GEO database, and qPCR confirmation was determined by collecting cartilage endplates from two groups. ACAN, Col2A1, p16, p21, and p53 were detected by immunofluorescence, Western blot and qPCR in human nucleus pulposus cells. Changes of cell senescence were detected. The binding of Hsa-miR-183-3p to ataxiatelangiectasia mutated protein was confirmed by dual luciferase reporter assay. Results. Degenerative discs showed elevated expression of hsa-miR-183-3p, which may be upregulated by TNF-α via NF-κB signaling pathway and target ataxiatelangiectasia mutated protein regulation. Conclusion. Degeneration of the intervertebral disc can be accelerated by TNF-α. Additionally, Hsa-miR- 183-3p passed NF-κB signaling pathway is blocked via upregulation of TNF-α to reduce inflammation via targeting ataxia-telangiectasia mutated protein. As a result, this negative feedback mechanism may assist in maintaining a low degenerative load and preserving chronic disc degeneration.

Keywords: hsa-miR-183-3p, ATM.

Correspondence: Qingshui Yin MD, General Hospital of Guangzhou Military Command Orthopedics Hospital, 111 Liuhua Rd, Yuexiu District, Guangzhou, Guangdong Province, 510010, China, E-mail: qingshuiY2022@163.com