# Circular RNA circMRPS35 represses malignant progression in osteosarcoma cells via targeting miR-105-5p/FOXO1

## TL;DR

This study shows that a circular RNA called circMRPS35 helps stop the spread of osteosarcoma cancer by interacting with miR-105-5p and FOXO1.

## Contribution

The study reveals a novel regulatory mechanism involving circMRPS35, miR-105-5p, and FOXO1 in osteosarcoma progression.

## Key findings

- Overexpression of circMRPS35 reduces osteosarcoma cell viability and tumor growth in vivo.
- circMRPS35 interacts with miR-105-5p to regulate FOXO1 expression and induce apoptosis in osteosarcoma cells.
- Inhibiting miR-105-5p or overexpressing FOXO1 counteracts the effects of circMRPS35 on cancer progression.

## Abstract

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 in vivo. 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.