Department of Immunology, College of Medicine, Yanbian University, Yanji, Jilin 133002, P.R. China.
Department of Spine Surgery, Jilin Central Hospital, Jilin 132011, P.R. China.
Aging (Albany NY). 2024 Aug 5;16(15):11568-11576. doi: 10.18632/aging.206022.
Osteosarcoma is a highly metastatic, aggressive bone cancer that occurs in children and young adults worldwide. Circular RNAs (circRNAs) are crucial molecules for osteosarcoma progression. In this study, we aimed to investigate the impact of circMRPS35 overexpression and its interaction with FOXO1 via evaluating apoptosis, cell cycle, and bioinformatic analyses on the malignant development of osteosarcoma in MG63 and MNNG/HOS cells. We found that circMRPS35 overexpression reduced osteosarcoma cell viability and inhibited tumor growth . It increased the apoptosis rate and induced cell cycle arrest in osteosarcoma cells. We identified a potential interaction between circMRPS35 and FOXO1 with miR-105-5p using bioinformatics analysis. Overexpression of circMRPS35 decreased miR-105-5p expression, whereas miR-105-5p mimic treatment increased its expression. This mimic also suppressed the luciferase activity of circMRPS35 and FOXO1 and reduced FOXO1 expression. Overexpression of circMRPS35 elevated FOXO1 protein levels, but this effect was reversed by co-treatment with the miR-105-5p mimic. We demonstrated that inhibiting miR-105-5p decreased viability and induced apoptosis. Overexpression of FOXO1 or treatment with a miR-105-5p inhibitor could counteract the effects of circMRPS35 on viability and apoptosis in osteosarcoma cells. Therefore, we concluded that circMRPS35 suppressed the malignant progression of osteosarcoma via targeting the miR-105-5p/FOXO1 axis.
骨肉瘤是一种高度转移性、侵袭性的骨癌,发生在全球儿童和青少年中。环状 RNA(circRNA)是骨肉瘤进展的关键分子。在这项研究中,我们旨在通过评估凋亡、细胞周期和生物信息学分析,研究 circMRPS35 过表达及其与 FOXO1 的相互作用对 MG63 和 MNNG/HOS 细胞骨肉瘤恶性发展的影响。我们发现 circMRPS35 过表达降低了骨肉瘤细胞的活力并抑制了肿瘤的生长。它增加了骨肉瘤细胞的凋亡率并诱导细胞周期停滞。我们通过生物信息学分析鉴定出 circMRPS35 和 FOXO1 与 miR-105-5p 之间的潜在相互作用。circMRPS35 的过表达降低了 miR-105-5p 的表达,而 miR-105-5p 模拟物处理则增加了其表达。该模拟物还抑制了 circMRPS35 和 FOXO1 的荧光素酶活性并降低了 FOXO1 的表达。circMRPS35 的过表达提高了 FOXO1 蛋白水平,但这一效应被 miR-105-5p 模拟物的共处理所逆转。我们证明了抑制 miR-105-5p 降低了细胞活力并诱导了凋亡。FOXO1 的过表达或 miR-105-5p 抑制剂的处理可以抵消 circMRPS35 对骨肉瘤细胞活力和凋亡的影响。因此,我们得出结论,circMRPS35 通过靶向 miR-105-5p/FOXO1 轴抑制骨肉瘤的恶性进展。