MicroRNA-181a Enhances Chemoresistance Of Human Cervical Squamous Cell Carcinoma To Cisplatin By Targeting PRKCD

PURPOSE:MicroRNAs (miRNAs) are involved in regulating the response of cancer cells to various therapeutic interventions, but their involvement in chemoresistance of human cervical squamous cell carcinoma is not fully understood. We found that miR-181a was significantly up-regulated in specimens from patients with chemoresistant cervical squamous cell carcinoma. In this study, we aimed to clarify the role of miR-181a in regulating the chemoresistance of cervical cancer.METHODS:Two human cervical squamous cell carcinoma cell lines, SiHa and Me180, were used in vitro and in vivo (xenograft tumor model in nude mice) studies. qRT-PCR assays were used to detect differential expression of miR-181a in cell lines. Cell viability was tested to evaluate the chemoresistance of cancer cells. Cell proliferation, apoptosis and cell cycle were quantified to validate the mechanism of chemoresistance induced by miR-181a.RESULTS:Up-regulation of miR-181a enhanced chemoresistance to cisplatin of cervical cancer cells through apoptosis reversion. In a nude mouse xenograft model, overexpression of miR-181a significantly inhibited therapeutic response to cisplatin. PRKCD, one target gene of miR-181a and a promoter of apoptosis, was negatively regulated by miR-181a. We found that the effect of miR-181a on chemoresistance was mediated by PRKCD. And knock-down of PRKCD yielded similar effect as that of up-regulation of miR-181a and caused apoptosis reversion.CONCLUSIONS:Our findings suggest that overexpression of miR-181a induced chemoresistance in cervical squamous cell carcinoma cells by down-regulating PRKCD, thus providing a biomarker for predicting the chemosensitivity and a potential target for reversing chemoresistance in cervical cancer.