title: MiR-9, -31, and -182 deregulation promote proliferation and tumor cell survival in colon cancer.
abstract: Several microRNAs (miRNAs) are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53) and apoptosis (n = 93). From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80) and normal colonic mucosa (n = 20). The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30) and polyps (n = 10) versus normal colonic mucosa (n = 10), whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival.
authors.affiliation: Department of Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Lina
authors.initials: L
authors.lastname: Cekaite
authors.forename: Juha K
authors.initials: JK
authors.lastname: Rantala
authors.forename: Jarle
authors.initials: J
authors.lastname: Bruun
authors.forename: Marianne
authors.initials: M
authors.lastname: Guriby
authors.forename: Trude H
authors.initials: TH
authors.lastname: Agesen
authors.forename: Stine A
authors.initials: SA
authors.lastname: Danielsen
authors.forename: Guro E
authors.initials: GE
authors.lastname: Lind
authors.forename: Arild
authors.initials: A
authors.lastname: Nesbakken
authors.forename: Olli
authors.initials: O
authors.lastname: Kallioniemi
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
authors.forename: Rolf I
authors.initials: RI
authors.lastname: Skotheim
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009857:Oncogenes; D015203:Reproducibility of Results
chemical_list: C534612:MIRN31 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human