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RNA virus microRNA that mimics a B-cell oncomiR.

ABSTRACT: MicroRNAs (miRNAs) are small RNAs that play a regulatory role in numerous and diverse eukaryotic cellular processes. Virus-encoded miRNAs have garnered much interest, although the functions of most remain to be deciphered. To date, readily detectable, evolutionarily conserved natural miRNAs have only been identified from viruses with DNA genomes. Combined with the fact that most miRNAs are generated from endonucleolytic cleavage of longer transcripts, this finding has led to a common conception that naturally occurring RNA viruses will not encode miRNAs to avoid unproductive cleavage of their genomes or mRNAs. Here we demonstrate that the bovine leukemia virus (BLV), a retrovirus with an RNA genome, encodes a conserved cluster of miRNAs that are transcribed by RNA polymerase III (pol III). Thus, the BLV miRNAs avoid the conundrum of genome/mRNA cleavage because only the subgenomic pol III transcripts are efficiently processed into miRNAs. BLV infection is strongly associated with B-cell tumors in cattle. Because most cells in BLV-associated tumors express little viral mRNAs or proteins, exactly how BLV contributes to tumorigenesis has remained a decades-long unsolved mystery. One BLV miRNA, BLV-miR-B4, shares partial sequence identity and shared common targets with the host miRNA, miR-29. As miR-29 overexpression is associated with B-cell neoplasms that resemble BLV-associated tumors, our findings suggest a possible mechanism contributing to BLV-induced tumorigenesis.

SUBMITTER: Kincaid RP

PROVIDER: S-EPMC3286953 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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RNA virus microRNA that mimics a B-cell oncomiR.

Kincaid Rodney P RP Burke James M JM Sullivan Christopher S CS

Proceedings of the National Academy of Sciences of the United States of America 20120130 8

MicroRNAs (miRNAs) are small RNAs that play a regulatory role in numerous and diverse eukaryotic cellular processes. Virus-encoded miRNAs have garnered much interest, although the functions of most remain to be deciphered. To date, readily detectable, evolutionarily conserved natural miRNAs have only been identified from viruses with DNA genomes. Combined with the fact that most miRNAs are generated from endonucleolytic cleavage of longer transcripts, this finding has led to a common conception ...[more]

PMID: 22308400

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Project description:Gastric cancer is one of the most common causes of death worldwide, although its incidence has steadily declined in recent years. There is strong evidence that aberrantly expressed microRNAs (miRNAs) are involved in gastric cancer tumorigenesis. Furthermore, CRMP4 is closely associated with the occurrence and development of gastric cancer, and our predictions suggest that miR-130a, which can promote gastric cancer tumorigenesis, is a potential CRMP4 regulator. In this study, we investigated the expression of CRMP4 and miR-130a in human gastric cancer cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) examination and direct interactions between miR-130a and CRMP4 by dual-luciferase reporter assay. We also evaluated the biological roles of miR-130a and CRMP4 in gastric cancer cells by flow cytometry, MTT assay, soft agar colony formation assay, and Transwell tests and confirmed CRMP4 function in vivo, using a tumor xenograft model. Our results demonstrated that CRMP4 expression was significantly decreased at both the gene and protein levels, while miR-130a expression was notably increased, in five human gastric cancer cell lines compared with human gastric epithelial cells. Dual-luciferase reporter assays indicated that CRMP4 was the direct target of miR-130a. Moreover, an inverse regulatory relationship between miR-130a and CRMP4 was verified by qRT-PCR and WB, and overexpression of miR-130a in BGC823 cells enhanced apoptosis and cell proliferation, arrested the cell cycle in G0/G1, and facilitated cell colony formation, invasion, migration, and adhesion, while upregulation of CRMP4 had opposite effects. Finally, the growth and weight of transplanted tumors derived from BGC823 cells in which CRMP4 was knocked down were remarkably reduced. These data indicate that miR-130a is an oncomir targeting CRMP4 and could be developed as a potential prognostic factor and a novel therapeutic target in gastric cancer.

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RNA virus microRNA that mimics a B-cell oncomiR.

Publications

RNA virus microRNA that mimics a B-cell oncomiR.

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