title: MicroRNA-301b promotes cell invasiveness through targeting TP63 in pancreatic carcinoma cells.
abstract: Recent studies have demonstrated that deregulated microRNA (miR) expression is implicated in the development of human cancers. In the aberrant miR expression, miR-301 is upregulated in cancers, such as pancreatic, colorectal and oral carcinoma. Based on this evidence, we investigated the contribution of miR-301 to pancreatic carcinoma and the novel target genes of miR-301 in pancreatic carcinoma. In this study, we analyzed the effects of enforced and inhibited expression of miR-301b expression in the Panc-1 and BxPC-3 cell lines. MiR-301b expression levels were associated with cell invasiveness in both cell lines. Additional experiments indicated that miR-301b influences invasiveness through CDH1. Moreover microRNA target search algorithms and experimental strategies suggested that miR-301b suppressed TP63 expression as a novel target of miR-301b. Remarkably, miR-301b was also found to be associated with NF-κB activity in both cell lines. In summary, overexpressed miR-301b may suppress TP63 expression and contributes to promote cell invasiveness and to enhance gemcitabine resistance in pancreatic carcinoma cells. Thus, miR-301b may have potential as a novel therapeutic target for cancer treatment due to its stimulatory effects on cell invasiveness.
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Naotake
authors.initials: N
authors.lastname: Funamizu
authors.affiliation: Howard University School of Medicine, Washington DC, USA.
authors.forename: Curtis Ray
authors.initials: CR
authors.lastname: Lacy
authors.affiliation: Georgetown University, Washington DC, USA.
authors.forename: Sonya T
authors.initials: ST
authors.lastname: Parpart
authors.affiliation: Department of Gastroenterology, Kyoto University, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takai
authors.affiliation: Department of Surgery, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukiharu
authors.initials: Y
authors.lastname: Hiyoshi
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanaga
mesh_terms: D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: C550735:MIRN301A microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D000093542:Gemcitabine