Abstract
Osteosarcoma is the most common primary bone malignancy found in children and young adults. Chemotherapy resistance, especially to cisplatin, presents a major clinical challenge in the treatment and prognosis of osteosarcoma. New biomarkers and mechanisms of cisplatin resistance in osteosarcoma are urgently needed due to poor survival outcomes and currently inadequate treatments. In this study, we investigate the role and potential mechanisms of microtubule-affinity regulating kinase2 (MARK2) during osteosarcoma cisplatin resistance. Gene Expression Omnibus dataset analyses indicated that high MARK2 expression was associated with poor prognosis and may positively correlate with chemoresistance. Moreover, we showed that MARK2 was significantly upregulated in osteosarcoma cells compared with normal cells. The overexpression and inhibition of MARK2 promoted and suppressed, respectively, cisplatin resistance in osteosarcoma cells in vitro and in vivo. Mechanistically, MARK2 overexpression enhanced P-glycoprotein expression and decreased cell apoptosis through PI3K/AKT/NF-κB signaling pathway activation, resulting in cisplatin resistance. Our results suggest that high MARK2 expression can enhance cisplatin resistance in osteosarcoma cells, supporting the potential of MARK2 as a new therapeutic target and biomarker for predicting cisplatin resistance in osteosarcoma.