Circular RNA LARP4 correlates with decreased Enneking stage, better histological response, and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging microRNA‐424 in osteosarcoma

BACKGROUND: This study aimed to evaluate the association of circular RNA La‐related RNA‐binding protein 4 (circ‐LARP4) with clinical features and prognosis in osteosarcoma patients, and further explore its effect on chemosensitivity in osteosarcoma cells. METHODS: Seventy‐two osteosarcoma patients with Enneking stage IIA‐IIB who underwent resection were consecutively enrolled, and then, tumor tissues and non‐tumor tissues were obtained. Circ‐LARP4 in tumor tissue/non‐tumor tissue was detected by quantitative polymerase chain reaction. After circ‐LARP4 overexpression and negative control overexpression plasmid transfection, relative cell viability (%) was evaluated by Cell Counting Kit‐8 in MG63 cells treated by different concentrations of cisplatin, methotrexate, and doxorubicin, and IC(50) was calculated. RESULTS: Circ‐LARP4 was downregulated in tumor tissue compared with non‐tumor tissue and had a good value in distinguishing tumor tissue from non‐tumor tissue with an area under curve of 0.829 (95% CI: 0.762‐0.859). Meanwhile, tumor circ‐LARP4 was negatively correlated with the Enneking stage. After resection, circ‐LARP4 high expression patients showed an increased tumor cell necrosis rate to adjuvant chemotherapy compared to circ‐LARP4 low expression patients, and circ‐LARP4 high expression correlated with prolonged disease‐free survival and overall survival. In vitro experiments revealed that circ‐LARP4 overexpression elevated the chemosensitivity of MG63 cells to cisplatin and doxorubicin but not methotrexate, with decreased cisplatin IC(50) and doxorubicin IC(50) concentrations than negative control. Besides, miR‐424 overexpression attenuated the chemosensitivity in circ‐LARP4 overexpression‐treated MG63 cells. CONCLUSION: Circ‐LARP4 high expression correlates with decreased Enneking stage and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging miR‐424 in osteosarcoma.