Li Renjie, He Huixian, He Xinxin
School of Nursing, Sun Yat-Sen University, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Exp Ther Med. 2023 Feb 23;25(4):163. doi: 10.3892/etm.2023.11862. eCollection 2023 Apr.
Osteosarcoma is the most prevalent primary malignant bone cancer worldwide. Apolipoprotein C1 (APOC1) and mitochondrial carrier homolog 2 (MTCH2) have been identified to be upregulated during the oncogenesis and metastasis of osteosarcoma. The aim of the present study was to explore the role of APOC1 in osteosarcoma progression and the mechanisms associated with MTCH2. APOC1 and MTCH2 expression in osteosarcoma cells was assessed by reverse transcription-quantitative PCR and western blotting. Then, APOC1 was silenced to detect its effect on cell viability, proliferation and apoptosis using Cell Counting Kit-8, a colony formation assay and TUNEL staining, respectively. Transwell and wound healing assays were used to evaluate cell invasion and migration. The interaction between APOC1 and MTCH2 as predicted by the Biological General Repository for Interaction Datasets and the Search Tool for the Retrieval of Interacting Genes/Proteins databases was verified by co-immunoprecipitation assay. Subsequently, rescue experiments were performed to analyze the regulatory effects of APOC1 on MTCH2 in the biological behavior and Warburg effect of osteosarcoma cells. Significantly upregulated APOC1 and MTCH2 expression was found in osteosarcoma SAOS-2 cells. APOC1 silencing attenuated cell viability, inhibited proliferation and promoted cell apoptosis, coupled with the decreased Bcl-2 expression and increased Bax and cleaved-caspase 3 expression. The invasive and migratory capacities of SAOS-2 cells were also suppressed following APOC1 knockdown. Moreover, APOC1 was confirmed to interact with MTCH2 in osteosarcoma cells. MTCH2 upregulation inhibited the impacts of APOC1 deletion on the malignant behavior of osteosarcoma cells. APOC1 silencing-induced oxidative phosphorylation elevation and Warburg effect decrease were partially restored by MTCH2 upregulation. In sum, APOC1 promoted progression of osteosarcoma by binding to MTCH2, suggesting that targeting the APOC1/MTCH2 axis may be a potential treatment of osteosarcoma.
骨肉瘤是全球最常见的原发性恶性骨癌。载脂蛋白C1(APOC1)和线粒体载体同源物2(MTCH2)已被证实在骨肉瘤的发生和转移过程中上调。本研究的目的是探讨APOC1在骨肉瘤进展中的作用以及与MTCH2相关的机制。通过逆转录定量PCR和蛋白质免疫印迹法评估骨肉瘤细胞中APOC1和MTCH2的表达。然后,分别使用细胞计数试剂盒-8、集落形成试验和TUNEL染色法沉默APOC1,以检测其对细胞活力、增殖和凋亡的影响。采用Transwell和伤口愈合试验评估细胞侵袭和迁移能力。通过免疫共沉淀试验验证了生物相互作用数据集通用存储库和检索相互作用基因/蛋白质数据库预测的APOC1和MTCH2之间的相互作用。随后,进行了挽救实验,以分析APOC1对骨肉瘤细胞生物学行为和瓦伯格效应中MTCH2的调控作用。在骨肉瘤SAOS-2细胞中发现APOC1和MTCH2表达显著上调。APOC1沉默减弱了细胞活力,抑制了增殖并促进了细胞凋亡,同时Bcl-2表达降低,Bax和裂解的半胱天冬酶-3表达增加。APOC1敲低后,SAOS-2细胞的侵袭和迁移能力也受到抑制。此外,证实APOC1在骨肉瘤细胞中与MTCH2相互作用。MTCH2上调抑制了APOC1缺失对骨肉瘤细胞恶性行为的影响。MTCH2上调部分恢复了APOC1沉默诱导的氧化磷酸化升高和瓦伯格效应降低。总之,APOC1通过与MTCH2结合促进骨肉瘤进展,表明靶向APOC1/MTCH2轴可能是骨肉瘤的一种潜在治疗方法。