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PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome.

ABSTRACT: Although PIWI-interacting RNAs (piRNAs) account for the largest class of the small non-coding RNA superfamily, virtually nothing is known of their function in human carcinogenesis. Once thought to be expressed solely in the germ line where they safeguard the genome against transposon-induced insertional mutations, piRNAs are now believed to play an active role in somatic gene regulation through sequence-specific histone modification and DNA methylation. In the current study, we investigate the role of piRNA-021285 (piR-021285) in the regulation of the breast cancer methylome. Genotypic screening of a panel of single-nucleotide polymorphism (SNP)-containing piRNAs revealed a significant association between SNP rs1326306 G>T in piR-021285 and increased likelihood for breast cancer in a Connecticut-based population (441 cases and 479 controls). Given nascent but compelling evidence of piRNA-mediated gene-specific methylation in the soma, a genome-wide methylation screen was then carried out using wild type (WT) and variant piR-021285 mimic-transfected MCF7 cells to explore whether the observed association could be attributed in part to piR-021285-induced methylation at cancer-relevant genes. We found significant methylation differences at a number of experimentally implicated breast cancer-related genes, including attenuated 5' untranslated region (UTR)/first exon methylation at the proinvasive ARHGAP11A gene in variant mimic-transfected cells. Follow-up functional analyses revealed both concurrent increased ARHGAP11A mRNA expression and enhanced invasiveness in variant versus WT piR-021285 mimic-transfected breast cancer cell lines. Taken together, our findings demonstrate the first evidence supporting a role of piRNAs, a novel group of non-coding RNA, in human tumorigenesis via a piRNA-mediated epigenetic mechanism, which warrants further confirmation and investigation.

SUBMITTER: Fu A

PROVIDER: S-EPMC5006152 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome.

Fu Alan A Jacobs Daniel I DI Hoffman Aaron E AE Zheng Tongzhang T Zhu Yong Y

Carcinogenesis 20150725 10

Although PIWI-interacting RNAs (piRNAs) account for the largest class of the small non-coding RNA superfamily, virtually nothing is known of their function in human carcinogenesis. Once thought to be expressed solely in the germ line where they safeguard the genome against transposon-induced insertional mutations, piRNAs are now believed to play an active role in somatic gene regulation through sequence-specific histone modification and DNA methylation. In the current study, we investigate the r ...[more]

PMID: 26210741

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Project description:PIWI-interacting RNAs (piRNAs) are a novel class of small ncRNAs initially isolated from germ line cells; although recent studies report that they are expressed also in somatic cells. To elucidate the role of piRNAs in somatic cells, in particular from breast cancer, we performed the first extensive next generation sequencing expression analysis of small RNA transcriptomes of hormone responsive breast cancer cell lines in different culture conditions. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GSE39162) database was used. Results led to the identification of ~100 and ~150 human piRNAs in the breast cancerous cell lines and tumors respectively, several of which differentially expressed in cell lines under different experimental conditions tested or in response to ERβ and in tumor tissues. Western blotting and Q-PCR analysis also revealed the presence in breast cell lines of PIWIL (PIWI Like) subfamily members proteins encoded in the human genome (PIWIL2/HILI and PIWIL4/HIWI2) and of other components of the piRNA biogenesis pathways, suggesting that this might indeed be functional in somatic cells. These results show that piRNAs are expressed in human somatic cells, in particular in cancer, where their expression is influenced by neoplastic transformation, growth conditions and estrogen receptor beta. More important, we demonstrate for the first time a distinct pattern of piRNAs expression in cancerous vs normal breast tissues, which suggests a potential role of these epigenetic modulators in mammary carcinogenesis and maintenance of the cancer cell phenotype. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GEO; GSM957192 TAX577740T ,GSM957194 TAX577740N, GSM957195 TAX577453T, GSM957197 TAX577453N, GSM957198 TAX577745T, GSM957200 TAX577745N, GSM957201 TAX577579T, GSM957203 TAX577579N) was used.

Dataset Information

PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome.

Publications

PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome.

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