title: The microRNA signature of patients with sunitinib failure: regulation of UHRF1 pathways by microRNA-101 in renal cell carcinoma.
abstract: Molecular targeted therapy is a standard treatment for patients with advanced renal cell carcinoma (RCC). Sunitinib is one of the most common molecular-targeted drugs for metastatic RCC. Molecular mechanisms of sunitinib resistance in RCC cells is still ambiguous. The microRNA (miRNA) expression signature of patients with sunitinib failure in RCC was constructed using a polymerase chain reaction (PCR)-based array. Several miRNAs that were aberrantly expressed in RCC tissues from patients treated with sunitinib were identified in this analysis. MicroRNA-101 (miR- 101) was markedly suppressed in sunitinib treated RCC tissues. Restoration of miR-101 significantly inhibited cell migration and invasion in Caki-1 and 786-O cells. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was directly suppressed by miR-101 in RCC cells, and overexpression of UHRF1 was confirmed in sunitinib-treated RCC tissues. The pathways of nucleotide excision repair and mismatch repair were significantly suppressed by knockdown of UHRF1. Our findings showed that antitumor miR-101- mediated UHRF1 pathways may be suppressed by sunitinib treatment.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurozumi
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States of America.
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.affiliation: Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Matsushita
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Department of Pathology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Pathology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Naya
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D035683:MicroRNAs / Q000235:genetics*; D011758:Pyrroles / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000235:genetics; D000077210:Sunitinib; D059467:Transcriptome; D017211:Treatment Failure; D044767:Ubiquitin-Protein Ligases
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D022762:CCAAT-Enhancer-Binding Proteins; D007211:Indoles; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D011758:Pyrroles; D034741:RNA, Small Interfering; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; D000077210:Sunitinib
keywords: UHRF1; miR-101; microRNA; renal cell carcinoma; sunitinib