The long non-coding RNA ANRASSF1 in the regulation of alternative protein-coding transcripts RASSF1A and RASSF1C in human breast cancer cells: implications to epigenetic therapy

摘要

Alternative protein-coding transcripts of the gene have been associated with dual functions in human cancer: while isoform has oncogenic properties, is a tumour suppressor frequently silenced by hypermethylation. Recently, the antisense long non-coding RNA RASSF1 ( was implicated in a -specific mechanism for the epigenetic repression mediated by PRC2 (Polycomb Repressive Complex 2). Here, we evaluated the methylation patterns of the promoter regions of and and the expression levels of these transcripts in breast cancer and breast cancer cell lines. As expected, remained unmethylated and was hypermethylated at high frequencies in 75 primary breast cancers, and also in a panel of three mammary epithelial cells (MEC) and 10 breast cancer cell lines (BCC). Although was expressed in all cell lines, only two of them expressed the transcript expression levels were increased in six BCCs. induced demethylation with 5-Aza-2ʹ-deoxicytydine (5-Aza-dC) resulted in up-regulation of and an inverse correlation with relative abundance in BCCs. However, increased levels of both transcripts were observed in two MECs (184A1 and MCF10A) after treatment with 5-Aza-dC. Overall, these findings indicate that is differentially expressed in MECs and BCCs. The lncRNA provides new perspectives as a therapeutic target for -specific regulation of .