title: Differential microRNA expression in aristolochic acid-induced upper urothelial tract cancers ex vivo.
abstract: Aristolochic acid (AA) is a carcinogenic, mutagenic and nephrotoxic compound commonly isolated from members of the plant family of Aristolochiaceae (such as Aristolochia and Asarum) and used in Chinese herbal medicine. Use of AA and AA‑containing plants causes chronic kidney disease (CKD) and upper urinary tract carcinoma (UUC); however, the underlying mechanism remains to be defined. miRNAs regulate a number of biological processes, including cell proliferation, differentiation and metabolism. This study explored differentially expressed miRNAs between AA‑induced upper urothelial tract cancer (AAN‑UUC) and non‑AAN‑UUC tissues. Patients with AAN‑UUC and non‑AAN‑UUC (n=20/group) were recruited in the present study. Five tissue samples from each group were used for miRNA microarray profiling and the rest of the tissue samples were subjected to reverse transcription-quantitative polymerase chain reaction analysis including seven selected miRNAs for confirmation. A total of 29 miRNAs were differentially expressed between AAN‑UUC and non‑AAN‑UUC tissues (P<0.05). TargenScan and Gene ontology analyses predicted the functions and targeted genes of these differentially expressed miRNAs, i.e. Akt3, FGFR3, PSEN1, VEGFa and AR. Subsequently, expression of the selected differentially expressed miRNAs (Hsa‑miR‑4795‑5p, Hsa‑miR‑488, Hsa‑miR‑4784, Hsa‑miR‑330, Hsa‑miR‑3916, Hsa‑miR‑4274 and Hsa‑miR‑181c) was validated in another set of tissue samples. A total of 29 miRNAs were identified to be differentially expressed between AAN‑UUC and non‑AAN‑UUC tissues and these miRNA target genes in FGFR3 and Akt pathways, which regulate cell growth and tumor progression, respectively.
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Jifu
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000368:Aged; D034341:Aristolochic Acids / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism; D014571:Urologic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D034341:Aristolochic Acids; D002273:Carcinogens; D035683:MicroRNAs; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012334:RNA, Neoplasm; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000228:aristolochic acid I; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt