title: miR-199a-3p inhibits aurora kinase A and attenuates prostate cancer growth: new avenue for prostate cancer treatment.
abstract: Prostate cancer (PCa) is the most common solid tumor malignancy in men that severely influences quality of life. Surgery is most often the recommended treatment for PCa, but radical prostatectomy can cause significant urinary adverse effects. Therefore, finding effective biochemical treatments for PCa remains a necessity. Aurora kinase A has been shown to be involved in PCa progression, thus making it a good target for PCa therapy. miRNAs are important regulators of gene expression, with some miRNAs specifically involved in carcinogenesis. Therefore, herein, we identified miRNAs targeted to aurora kinase A and examined their effects on the growth of PCa. We used primary samples from PCa patients and PCa cell lines as research subjects. We demonstrate that miR-199a-3p is down-regulated in PCa tissues compared with normal prostate tissues, with the expression pattern inversely correlated with the expression pattern of aurora kinase A. We find that miR-199a-3p agomir inhibits aurora kinase A and attenuates xenograft tumor growth of PCa. Moreover, we demonstrate that down-regulation of miR-199a-3p results from enhancement of the methylation of miR-199a gene in PCa. Furthermore, we find that the expression level of miR-199a-3p is inversely correlated to tumor stage and Gleason score of PCa. Revealing novel mechanisms for oncogene inhibition by miRNA-mediated pathways offers new avenues for PCa treatment.
authors.affiliation: Key Laboratory of Birth Defects of Ministry of Education, Sichuan University, Chengdu, China. Electronic address: quyi712002@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Urology, The People's Hospital of Sichuan Province, Chengdu, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Urology, The People's Hospital of Sichuan Province, Chengdu, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Birth Defects of Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Birth Defects of Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Birth Defects of Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Laboratory of Birth Defects of Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Birth Defects of Ministry of Education, Sichuan University, Chengdu, China. Electronic address: mudz@scu.edu.cn.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001374:Azacitidine / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D049449:Luminescence; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; C531408:mirn199 microRNA, human; D008156:Luciferases; C576917:AURKA protein, human; D064096:Aurora Kinase A; D001374:Azacitidine