title: MicroRNA-181a enhances the chemoresistance of human cervical squamous cell carcinoma to cisplatin by targeting PRKCD.
abstract: MicroRNAs(miRNAs) are involved in regulating the response of cancer cells to various therapeutic interventions, but their involvement in the chemoresistance of human cervical squamous cell carcinoma is not fully understood. We found 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. Two human cervical squamous cancer cell lines, SiHa and Me180, were used. Enforced expression of miR-181a enhanced chemoresistance to cisplatin in cervical cancer cells through apoptosis reversion. In a nude mouse xenograft model, the overexpression of miR-181a markedly inhibited the therapeutic response to cisplatin. PRKCD, a 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. Additionally, silencing of PRKCD yielded an effect similar to that of miR-181a up-regulation and inhibited apoptosis in cervical cancer cells. Our findings suggest that miR-181a may function as an oncogene and induce chemoresistance in cervical squamous cell carcinoma cells at least in part by down-regulating PRKCD, thus may provide a biomarker for predicting chemosensitivity to cisplatin in patients with cervical squamous cancer.
authors.affiliation: Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai 200032, PR China; Department of Gynecologic Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing 100021, PR China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Chen
authors.forename: Guihao
authors.initials: G
authors.lastname: Ke
authors.forename: Duo
authors.initials: D
authors.lastname: Han
authors.forename: Shanhui
authors.initials: S
authors.lastname: Liang
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D015854:Up-Regulation / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta; D002945:Cisplatin
keywords: Apoptosis; Cervical cancer; Chemotherapy; Cisplatin; PRKCD; miR-181a