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MiR-486-5p Downregulation Marks an Early Event in Colorectal Carcinogenesis.

ABSTRACT: BACKGROUND:MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease. OBJECTIVE:The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages. DESIGN:A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis. SETTING:Genome-wide microRNA expression profiling was performed. PATIENTS:A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included. MAIN OUTCOME MEASURES:MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor. RESULTS:A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01). LIMITATIONS:Our microRNA profile was generated in a small subset of patients and will require validation in more samples. CONCLUSIONS:We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.

SUBMITTER: Kelley KA

PROVIDER: S-EPMC6172144 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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MiR-486-5p Downregulation Marks an Early Event in Colorectal Carcinogenesis.

Kelley Katherine A KA Wieghard Nicole N Chin Yuki Y Potter Amiee A Mori Motomi M Wong Melissa H MH Chin Koei K Tsikitis V Liana VL

Diseases of the colon and rectum 20181101 11

<h4>Background</h4>MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease.<h4>Objective</h4>The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages.<h4>Design</h4>A microRNA profile was generated and then explored in no ...[more]

PMID: 30239392

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Project description:Abnormal expression of microRNA (miR) is associated with the occurrence and progression of various types of cancers, including papillary thyroid carcinoma (PTC). In the present study, the aim was to explore miR?486?5p expression and its role in PTC, as well as to investigate the biological function of its potential target genes. The expression levels of miR?486?5p and its clinicopathological significance were examined in 507 PTC and 59 normal thyroid samples via The Cancer Genome Atlas (TCGA). Subsequently, the results were validated using data from Gene Expression Omnibus (GEO) and ArrayExpress. Receiver operating characteristic and summary receiver operating characteristic curves were used to assess the ability of miR?486?5p in distinguishing PTC from normal tissue. Furthermore, potential miR?486?5p mRNA targets were identified using 12 prediction tools and enrichment analysis was performed on the encoding genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The expression levels of miR?486?5p were consistently downregulated in PTC compared with in normal tissue across datasets from TCGA, GEO (GSE40807, GSE62054 and GSE73182) and ArrayExpress (E?MTAB?736). The results also demonstrated that miR?486?5p expression was associated with cancer stage (P=0.003), pathologic lymph node (P=0.047), metastasis (P=0.042), neoplasm (P=0.012) and recurrence (P=0.016) in patients with PTC. In addition, low expression of miR?486?5p in patients with PTC was associated with a worse overall survival. A total of 80 miR?486?5p?related genes were observed from at least 9 of 12 prediction platforms, and these were involved in 'hsa05200: Pathways in cancer' and 'hsa05206: MicroRNAs in cancer'. Finally, three hub genes, CRK like proto?oncogene, phosphatase and tensin homolog and tropomyosin 3, were identified as important candidates in tumorigenesis and progression of PTC. In conclusion, it may be hypothesized that miR?486?5p contributes towards PTC onset and progression, and may act as a clinical target. However, in vitro and in vivo experiments are required to validate the findings of the present study.

Dataset Information

MiR-486-5p Downregulation Marks an Early Event in Colorectal Carcinogenesis.

Publications

MiR-486-5p Downregulation Marks an Early Event in Colorectal Carcinogenesis.

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