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Mechanism analysis of colorectal cancer according to the microRNA expression profile.

ABSTRACT: The present study aimed to identify specific microRNAs (miRs) and their predicted target genes to clarify the molecular mechanisms of colorectal cancer (CRC). An miR expression profile (array ID, GSE39833), which consisted of 88 CRC samples with various tumor-necrosis-metastasis stages and 11 healthy controls, was downloaded from the Gene Expression Omnibus database. Subsequently, the differentially expressed miRs and their target genes were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways of target genes were analyzed using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the target genes was constructed using the Search Tool for the Retrieval of Interacting Genes database. The present study identified a total of 18 differentially expressed miRs (upregulated, 8; downregulated, 10) in the sera of the CRC patients compared with the healthy controls. Of these, 3 upregulated (let-7b, miR-1290 and miR-126) and 2 downregulated (miR-16 and miR-760) differentially expressed miRs and their target genes, including cyclin D1 (CCND1), v-myc avian myelocytomatosis viral oncogene homolog (MYC), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (PIK3R2) and SMAD family member 3 (SMAD3), were significantly enriched in the CRC developmental pathway. All these target genes had higher node degrees in the PPI network. In conclusion, let-7b, miR-1290, miR-126, miR-16 and miR-760 and their target genes, CCND1, MYC, PIK3R2 and SMAD3, may be important in the molecular mechanisms for the progression of CRC.

SUBMITTER: Li H

PROVIDER: S-EPMC5038387 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Mechanism analysis of colorectal cancer according to the microRNA expression profile.

Li Hong H Zhang Huichao H Lu Gang G Li Qingjing Q Gu Jifeng J Song Yuan Y Gao Shejun S Ding Yawen Y

Oncology letters 20160816 4

The present study aimed to identify specific microRNAs (miRs) and their predicted target genes to clarify the molecular mechanisms of colorectal cancer (CRC). An miR expression profile (array ID, GSE39833), which consisted of 88 CRC samples with various tumor-necrosis-metastasis stages and 11 healthy controls, was downloaded from the Gene Expression Omnibus database. Subsequently, the differentially expressed miRs and their target genes were screened. Gene Ontology and Kyoto Encyclopedia of Gene ...[more]

PMID: 27698796

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Project description:Background: circRNAs, a recently identified new member of non-coding RNAs, have been proved to play an essential role in the development and progression of various cancers. However, the functions and mechanisms of circRNAs in colorectal liver metastasis have not been fully elucidated. Methods: We performed circRNA microarray to screen differentially expressed novel circRNAs in the pathology of colorectal liver metastasis. Quantitative real-time PCR was used to detect the circ102049 expression in colorectal cancer (CRC) samples. Then CRC cells were transfected with a circ102049 over-expression vector or siRNAs, and the effects of circ102049 on biological functions in CRC cells were accessed in vitro. Mechanistically, the bioinformatics analysis, fluorescence in situ hybridization, RIP assay, RNA pull down assay and luciferase reporter assay were conducted to confirm the relationships among circ102049, miR-761, miR-192-3p and FRAS1. Moreover, the mechanism of circ102049 how to recruit and distribute DGCR8 protein in cytoplasm was elucidated. Results: The results showed that circ102049 was highly expressed in primary CRC tumors with liver metastasis and closely correlated with the CRC patients' prognosis. Circ102049 might act as a novel metastasis-related non-coding RNA, and significantly promote the adhesion, migration and invasion abilities of CRC cells. Mechanistically, we verified that circ102049 promoted the CRC development and progression via a miR-761/miR-192-3p-FRAS1-dependent mechanism. Notably, due to the distribution of DGCR8 protein, circ102049 might also reduce the mature products of miR-761 and miR-192-3p in cytoplasm indirectly. In addition, the role of circ102049 in promoting colorectal liver metastasis was also confirmed in vivo. Conclusions: Our findings provided new clues that circ102049 might be a potential prognostic factor in CRC, and the circ102049-miR-761/miR-192-3p-FRAS1 axis could be further explored as a therapeutic target for anti-metastatic therapy in CRC patients with liver metastases. Keywords: Hsa_circ_102049, miR-761, miR-192-3p, FRAS1, Colorectal liver metastasis

Dataset Information

Mechanism analysis of colorectal cancer according to the microRNA expression profile.

Publications

Mechanism analysis of colorectal cancer according to the microRNA expression profile.

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