CircAP1M2(hsa＿circ＿0049282) Induces Cisplatin Resistance Of Oral Squamous Cell Carcinoma Via Activating Autophagy

Background:Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck.Cisplatin(CDDP)is the first-line chemotherapeutic agent for OSCC,and its susceptibility to drug resistance during treatment is a major challenge in enhancing the therapeutic efficacy of OSCC.Autophagy is regarded as an essential element to guarantee the survival of cancer cells under chemo-stress conditions.We aim to investigate the role of circAP1M2 on autophagy and cisplatin resistance in OSCC.Methods : We established a cisplatin-resistant OSCC cell line(CAL27/CDDP)and determined the relative expression of circAP1M2 in cisplatin-resistant cells and their parental cells by qRT-PCR.The knockdown or forced overexpression of circAP1M2 was combined with in vitro and in vivo experiments such as CCK-8 assay,flow cytometry and xenograft experiments to demonstrate the functional role of circAP1M2 in OSCC.The effect of circAP1M2 on autophagy was evaluated by Western Blot,Transmission Electron Microscopy,and Immunofluorescence.And we used the bioinformatics method for detecting and analyzing the downstream target miRNAs of circAP1M2.Results:1.circAP1M2 is a remarkably upregulated circular RNA in OSCC;2.circAP1M2 is highly expressed in cisplatin-resistant OSCC cells;3.Knockdown of circAP1M2 contributes to reversing cisplatin chemoresistance in vivo;4.Enhanced autophagic activity in cisplatin-resistant OSCC cells contributes to the chemoresistance;5.circAP1M2 induces autophagy-associated cisplatin resistance in OSCC cells in vitro;6.circAP1M2 acts as a miRNA sponge and can specifically adsorb miR-1249-3p;7.circAP1M2/miR-1249-3p mediates cisplatin resistance in OSCC cells through autophagy.Conclusions:1.circAP1M2 enhances cisplatin resistance in OSCC cells by promoting autophagy;2.circAP1M2 sponges miR-1249-3p to regulate autophagy and mediate cisplatin resistance in OSCC.