Silencing RIF1 decreases cell growth migration and increases cisplatin sensitivity of human cervical cancer cells

摘要

Replication timing regulatory factor 1 (RIF1) plays an important role in DNA replication regulation, stem cell pluripotency and DNA repair pathway. However, little is known about the molecular mechanisms and physiological significance of RIF1 in cancer and chemotherapy efficacy. In this study, we found that RIF1 is upregulated in cervical cancer tissues compared with normal tissues both at mRNA and protein levels through online databases. RIF1 knockdown reduced cervical cancer cell growth, colony formation, migration and epithelial–mesenchymal transition (EMT) markers. Flow cytometry analysis indicated that RIF1 knockdown induced apoptosis and G2 cell cycle arrest. Furthermore, RIF1 knockdown increased cisplatin sensitivity, cisplatin-induced G2/M phase arrest, apoptosis and led to defects in DNA repair in a concentration-dependent manner. In terms of mechanism research, increased CDKN1A expression and Bax/Bcl-2/caspase-3 signaling pathway might be involved in the G2/M phase arrest and increased apoptosis in RIF1-silenced cervical cancer cells. Thus, these findings indicate that RIF1 knockdown prior to chemotherapy may be a potential effective therapeutic strategy for cervical cancer.