In cancer cells, transcriptional gene silencing has been associated with genetic and epigenetic defects. The disruption of DNA methylation patterns and covalent histone marks has been associated with cancer development. Until recently, microRNA (miRNA) gene silencing was not well understood. In particular, miR-125b1 has been suggested to be a miRNA with tumor suppressor activity, and it has been shown to be deregulated in various human cancers. In this study, we characterized the promoter of the miR-125b1 and the modifications associated with gene silencing. We studied in silico the miR-125b1 locus to delimit the promoter region and then, we characterized the promoter activity by the luciferase assay, cloning a fragment in the 5′ extreme close to the transcriptional start site of the miR-125b1 gene. We found that this sequence has promoter activity and it is unidirectional. Subsequently, we analyzed the DNA methylation status in the CpG island promoter and found that it was methylated in breast cancer cell lines compared with a non-transformed breast cell line. To determine the effect of DNA methylation in the CpG island of miR-125b1 on the expression of this gene, we performed a qRT-PCR assay. We observed a significant reduction on the expression of miR-125b1 in cancer cells lines in comparison with a non-transformed cell line, suggesting that DNA methylation at the CpG island might reduce the expression of miR-125b1. Our data suggest that the fragment in the 5′ extreme close to the transcriptional start site of the miR-125b1 gene is a functional and unidirectional promoter. Also, the CpG island in this region is methylated in breast cancer cell lines and this methylation is associated with the silencing of the miR-125b1 gene. This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT: 83959) and the Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica of the Universidad Nacional Autónoma de México (PAPIIT, IN213311). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5041. doi:1538-7445.AM2012-5041
In this study we aim to identify new lncRNAs, using RNA-seq data, and study whether those transcripts could be involved in chromosomal instability in prostate cancer and propose new possible RNA-based biomarkers. Using RNA-seq data from two prostate cell lines, neoplastic and non-neoplastic, we have identified a new lncRNA adjacent to CEP55, a gene associated with chromosomal instability. This lncRNA, which we have named lncRNA-CEP55, is 1.6 kb long and it is downregulated in the neoplastic cell line; this is also seen in the adjacent coding gene, CEP55, where the expression decreases in the neoplastic line, suggesting an important role of this transcript in carcinogenesis. This new lncRNA could be regulating CEP55 expression in these cell lines. Changes in expression of CEP55 have been associated to chromosomal instability and cancer development in colon cancer cell lines. Another lncRNA with differential expression in both cell lines has been identified, lncRNA-RFC4. This lncRNA has been reported before; it is an annotated gene in the human genome GRCh38/hg38, but it has not been studied in cancer. This lncRNA is highly expressed in the neoplastic cell line whereas its expression is very low in the non-neoplastic cell line. This lncRNA is 4.3 kb away from RFC4 (Replication Factor C Subunit 4), a protein coding gene related to mismatch repair and DNA double-strand break repair, which has been associated with chromosomal instability. lncRNA-RFC4 could be playing an important role in the cis regulation of RFC4 gene. lncRNA-CEP55 and lncRNA-RFC4 are important targets of study because of their differential expression in prostate cell lines (neoplastic and non-neoplastic). These lncRNAs could be playing an essential role in regulating the expression of the adjacent genes related to chromosomal instability, a enabling characteristic that facilitates the acquisition of the hallmarks of cancer. Citation Format: Rogelio Montiel Manriquez, Cristian Gabriel Oliverio Arriaga Canon, Fernanda Cisneros Soberanis, Carlo César Cortés, Inti Alberto De La Rosa Velazquez, Luis Alonso Herrera Montalvo. Identification of lncRNAs involved in regulation of chromosome instability-associated genes in a prostate cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2474.
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