title: miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer.
abstract: The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using DharmaconTM microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value<0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P<0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC.
authors: Department of Pathology, School of Medicine, Scientific and Technological Bioresource Nucleus (BIOREN-CEGIN), Universidad de La Frontera Manuel Montt 112, Postal Code 4781176, Temuco, Chile ; School of Health Sciences, Universidad Católica de Temuco Manuel Montt 56, Postal Code 4813302, Temuco, Chile.
authors: Pablo
authors: P
authors: Letelier
authors: Department of Pathology, School of Medicine, Center of Translational Research in Oncology, Pontificia Universidad Católica de Chile Portugal 61, Postal Code 8330034, Santiago, Chile.
authors: Patricia
authors: P
authors: García
authors: Department of Pathology, School of Medicine, Scientific and Technological Bioresource Nucleus (BIOREN-CEGIN), Universidad de La Frontera Manuel Montt 112, Postal Code 4781176, Temuco, Chile.
authors: Pamela
authors: P
authors: Leal
authors: MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors: Héctor
authors: H
authors: Álvarez
authors: Department of Pathology, School of Medicine, Scientific and Technological Bioresource Nucleus (BIOREN-CEGIN), Universidad de La Frontera Manuel Montt 112, Postal Code 4781176, Temuco, Chile.
authors: Carmen
authors: C
authors: Ili
authors: Department of Pathology, School of Medicine, Scientific and Technological Bioresource Nucleus (BIOREN-CEGIN), Universidad de La Frontera Manuel Montt 112, Postal Code 4781176, Temuco, Chile.
authors: Jaime
authors: J
authors: López
authors: Department of Pathology, School of Medicine, Scientific and Technological Bioresource Nucleus (BIOREN-CEGIN), Universidad de La Frontera Manuel Montt 112, Postal Code 4781176, Temuco, Chile.
authors: Jonathan
authors: J
authors: Castillo
authors: Department of Pathology, School of Medicine, Scientific and Technological Bioresource Nucleus (BIOREN-CEGIN), Universidad de La Frontera Manuel Montt 112, Postal Code 4781176, Temuco, Chile.
authors: Priscilla
authors: P
authors: Brebi
authors: Department of Pathology, School of Medicine, Center of Translational Research in Oncology, Pontificia Universidad Católica de Chile Portugal 61, Postal Code 8330034, Santiago, Chile.
authors: Juan Carlos
authors: JC
authors: Roa
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D016000:Cluster Analysis; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: C544547:MIRN1 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: Gallbladder cancer; NOZ cells; miR-1; miR-145; microRNAs