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.
Keywords: Warburg effect; apolipoprotein C1; invasion; mitochondrial carrier homolog 2; osteosarcoma.
Copyright: © Li et al.