title: miRNA-100 inhibits human bladder urothelial carcinogenesis by directly targeting mTOR.
abstract: miRNAs are involved in cancer development and progression, acting as tumor suppressors or oncogenes. In this study, miRNA profiling was conducted on 10 paired bladder cancer tissues using 20 GeneChip miRNA Array, and 10 differentially expressed miRNAs were identified in bladder cancer and adjacent noncancerous tissues of any disease stage/grade. After being validated on expanded cohort of 67 paired bladder cancer tissues and 10 human bladder cancer cell lines by quantitative real-time PCR (qRT-PCR), it was found that miR-100 was downregulated most significantly in cancer tissues. Ectopic restoration of miR-100 expression in bladder cancer cells suppressed cell proliferation and motility, induced cell-cycle arrest in vitro, and inhibited tumorigenesis in vivo both in subcutaneous and in intravesical passage. Bioinformatic analysis showed that the mTOR gene was a direct target of miR-100. siRNA-mediated mTOR knockdown phenocopied the effect of miR-100 in bladder cancer cell lines. In addition, the cancerous metastatic nude mouse model established on the basis of primary bladder cancer cell lines suggested that miR-100/mTOR regulated cell motility and was associated with tumor metastasis. Both mTOR and p70S6K (downstream messenger) presented higher expression levels in distant metastatic foci such as in liver and kidney metastases than in primary tumor. Taken together, miR-100 may act as a tumor suppressor in bladder cancer, and reintroduction of this mature miRNA into tumor tissue may prove to be a therapeutic strategy by reducing the expression of target genes.
authors.affiliation: Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
authors.forename: Qinsong
authors.initials: Q
authors.lastname: Zeng
authors.forename: Weidong
authors.initials: W
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Jiao
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chengyao
authors.initials: C
authors.lastname: Wu
authors.forename: Taile
authors.initials: T
authors.lastname: Jin
authors.forename: Anyin
authors.initials: A
authors.lastname: Pan
authors.forename: Rongchao
authors.initials: R
authors.lastname: Wei
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: C544266:MIRN100 microRNA, human; D035683:MicroRNAs; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases