title: miR-106a overexpression and pRB downregulation in sporadic colorectal cancer.
abstract: Rb1 plays an important role in cell cycle progression and therefore may be involved in malignant transformation of colonic cells. The aim of our research was to define the potential role of Rb1 as a prognostic biomarker in tumorigenesis of sporadic colorectal cancer, and to examine the role of miR-106a in Rb1 regulation as it functionally binds to 3'UTR of transcribed mRNA. We examined LOH and promoter methylation status. Real-time PCR was used for Rb1 mRNA and miR-106a, and immunohistochemistry for protein expression analysis. All the results obtained from patients' samples were correlated with the clinicopathological parameters in order to determine its influence on the sporadic colorectal carcinogenesis. LOH showed no correlation with mRNA and pRb expression. 51.5% of tumor samples were scored negative for pRb staining. Despite this finding, we detected overexpression of Rb1 mRNA in tumor samples in comparison to the adjacent normal tissue (p=0.023). mRNA overexpression was consistent with Rb1 promoter methylation analysis results, which showed no methylation in the investigated samples. Expression analysis of miR-106a in the patients samples showed its overexpression in colorectal cancer (p<10(-4)). Negative pRb score was expected according to the definition of tumor suppressor genes and their proposed role in the malignant transformation of the cells. The observed discrepancy between mRNA and protein expression can be explained by a regulatory mechanism that inhibits translation, such as microRNA silencing. Our results suggest that miR-106a might have a regulatory role for Rb1 in sporadic colorectal cancer.
authors.affiliation: Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka c. 54, Zagreb, Croatia. tcatela@irb.hr
authors.forename: T
authors.initials: T
authors.lastname: Catela Ivkovic
authors.forename: G
authors.initials: G
authors.lastname: Aralica
authors.forename: T
authors.initials: T
authors.lastname: Cacev
authors.forename: B
authors.initials: B
authors.lastname: Loncar
authors.forename: S
authors.initials: S
authors.lastname: Kapitanovic
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002453:Cell Cycle; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016160:Retinoblastoma Protein