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 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. in tumor tissue/non-tumor tissue was detected by quantitative polymerase chain reaction. After 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 IC₅₀ was 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-Lduanyu374 was negatively correlated with the Enneking stage. After resection, circ-Lduanyu374 high expression patients showed an increased tumor cell necrosis rate to adjuvant chemotherapy compared to circ-Lduanyu374 low expression patients, and circ-Lduanyu374 high expression correlated with prolonged disease-free survival and overall survival. In vitro experiments revealed that circ-Lduanyu374 overexpression elevated the chemosensitivity of MG63 cells to cisplatin and doxorubicin but not methotrexate, with decreased cisplatin IC₅₀ and doxorubicin IC₅₀ concentrations than negative control. Besides, miR-424 overexpression attenuated the chemosensitivity in circ-Lduanyu374 overexpression-treated MG63 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.

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