Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway

Cervical cancer is the fourth most common cancer in women globally. Lack of effective pharmacotherapies for cervical cancer mainly attributed to an elusive understanding of the 8 mechanism underlying its pathogenesis. Pyroptosis plays a key role in inflammation and cancer. Our study identified microRNA (miR) 145 (miR-145)/gasdermin D (GSDMD) signaling pathway as critical mediators in the effect of tanshinone II A on HeLa cells. In the present study, we found that treatment of tanshinone II A led to an obvious repression of cell proliferation and an increase in apoptosis on HeLa cells, especially in high concentration. Compared with the controlled group, tanshinone II A enhanced the activity of caspase3 and caspase9. Notably, the results demonstrated that tanshinone II A regulated cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway. Treatment of tanshinone 11 A significantly up-regulated the expression of GSDMD and miR-145. After transfection of si-miR-145 plasmids, the effects of tanshinone II A on HeLa cells were converted, including cell proliferation, apoptosis and pyroptosis. In addition, the results showed that tanshinone II A treatment altered the expression level of PIK p-Akt, NF-kB p65 and Lc3-I. Collectively, our findings demonstrate that tanshinone II A exerts anticancer activity on HeLa cells by regulating miR-145/GSDMD signaling. The present study is the first time to identify miR-145 as a candidate target in cervical cancer and show an association between miR-145 and pyroptosis, which provides a novel therapy for the treatment of cervical cancer.