A tumor-promotional molecular axis CircMAPKBP1/miR-17-3p/TGFβ2 activates autophagy pathway to drive tongue squamous cell carcinoma cisplatin chemoresistance

Abstract

Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFβ2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFβ2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFβ2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.