预后相关的 VDAC1 通过 MAPK 信号通路调节骨肉瘤细胞的增殖和凋亡。

Prognosis-related VDAC1 regulates the proliferation and apoptosis of osteosarcoma cells via the MAPK signaling pathway.

机构信息

Department of Orthopedics, The Third Xiangya Hospital of Central South University, Changsha 410000, China.

Department of General Surgery, the Third Xiangya Hospital of Central South University, Changsha 410000, China.

出版信息

Genomics. 2023 May;115(3):110595. doi: 10.1016/j.ygeno.2023.110595. Epub 2023 Mar 5.

DOI:10.1016/j.ygeno.2023.110595

PMID:36871636

Abstract

The role of VDAC1 in osteosarcoma is unclear. We explored the effect of VDAC1 on osteosarcoma development by combining bioinformatic analysis and experimental identification. This study suggested that VDAC1 is an independent prognostic factor for osteosarcoma. Patients with high VDAC1 expression have a poor survival rate. VDAC1 was overexpressed in osteosarcoma cells. After silencing VDAC1, the proliferation of osteosarcoma cells decreased, and the apoptosis rate increased. Gene set variation analysis and gene set enrichment analysis indicated that VDAC1 was associated with the MAPK signaling pathway. After VDAC1 siRNA, SB203580 (a p38 inhibitor), SP600125 (a JNK inhibitor) and α-pifithrin (a p53 inhibitor) treatment, the proliferative capacity was weaker in the si-VDAC1 group than in the si-VDAC1 + SB203580, si-VDAC1 + SP600125, and si-VDAC1 + α-pifithrin groups. In conclusion, prognosis-related VDAC1 can affect osteosarcoma cells' proliferative activity and apoptosis level. The MAPK signaling pathway mediates VDAC1 regulation of osteosarcoma cell development.

摘要

VDAC1 在骨肉瘤中的作用尚不清楚。我们通过结合生物信息学分析和实验鉴定来研究 VDAC1 对骨肉瘤发生的影响。本研究提示 VDAC1 是骨肉瘤的一个独立预后因素。VDAC1 高表达的患者生存率较低。VDAC1 在骨肉瘤细胞中呈过表达。沉默 VDAC1 后，骨肉瘤细胞的增殖减少，凋亡率增加。基因集变异分析和基因集富集分析表明 VDAC1 与 MAPK 信号通路有关。VDAC1 siRNA 后，用 SB203580（p38 抑制剂）、SP600125（JNK 抑制剂）和 α-pifithrin（p53 抑制剂）处理，si-VDAC1 组的增殖能力弱于 si-VDAC1+SB203580、si-VDAC1+SP600125 和 si-VDAC1+α-pifithrin 组。综上所述，与预后相关的 VDAC1 可影响骨肉瘤细胞的增殖活性和凋亡水平。MAPK 信号通路介导 VDAC1 对骨肉瘤细胞发育的调节。