ARID1A-mutated cervical cancer depends on the activation of YAP signaling

Abstract

Background: Cervical cancer is a prevalent female malignancy with poor survival rates. ARID1A is frequently mutated or deleted in a variety of tumors and YAP signaling is widely activated in human malignancies. Nevertheless, the mechanism of YAP signaling in ARID1A-mutated cervical cancer remains unknown. Methods: The cell viability was determined by MTT assay. The expression of ARID1A, YAP1 and CTGF were evaluated by western blot. The cell proliferation was detected by colony formation. Results: The bioinformatics analysis suggested that mutation of ARID1A was associated with the activation of YAP1 signaling. In addition, knockdown of YAP1 inhibited ARID1A-mutated cervical cancer cells growth. Verteporfin is an inhibition of YAP1 signaling. Interestingly, knockdown of ARID1A decreased ARID1A-wildtype cervical cancer cells resistance to verteporfin. Meanwhile, overexpression of ARID1A increased ARID1A-mutated cervical cancer cells resistance to verteporfin. Similarly, blocking YAP1 signaling inhibited the tumor formation caused by ARID1A-mutated cervical cancer cells in vivo. Conclusion: Inhibition of YAP1 signaling suppresses ARID1A-mutated-induced tumorigenesis of cervical cancer, providing a novel therapeutic strategy for cervical cancer.

Keywords

• cervical cancer
• arid1a
• proliferation
• yap signaling