title: MicroRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor in cervical cancer.
abstract: We previously reported that microRNA-218 was frequently lost in cervical cancer and restoration of microRNA-218 increased cellular radio-sensitivity via inhibiting. Herein, we aim to investigate the effects of microRNA-218 on cellular response to mTOR inhibition. The expression of microRNA-218 and Rictor were measured by Taqman PCR and real time PCR in a panel of 15 cervical cancer tissues. MicroRNA-218 was stably overexpressed in four cervical cancer cell lines and a series of in vitro and in vivo experiments were performed to investigate cellular sensitivity to Rapamycin. In primary cultured cervical cancer cells, the expression of microRNA-218 was negatively correlated with the mRNA level of Rictor, which predicted cellular sensitivity to Rapamycin (p = 0.002, R(2)  = 0.6810). In vitro, overexpression of microRNA-218 significantly reduced the level of Rictor and enhanced the growth-inhibition, cell cycle arrest, and apoptosis induced by Rapamycin. In vivo, overexpression of microRNA-218 further enhanced the suppressive effects of Rapamycin on tumor growth. In conclusion, we demonstrated that microRNA-218 could re-sensitize cervical cancer to Rapamycin through targeting Rictor. Moreover, patients with loss of microRNA-218 presented notable resistance to Rapamycin, indicating that microRNA-218 might be a valid marker for patients-stratification in future clinical trials.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Li
authors.affiliation: Special Inspection Department, Yantai Longkuang center Hospital, Yantai, China.
authors.forename: Jingpu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University, Wuxi, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D020123:Sirolimus / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002352:Carrier Proteins; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; C492571:RICTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D020123:Sirolimus
keywords: MicroRNA-218; Rictor; cervical cancer; mTOR signal pathway; mTORC1; mTORC2