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

• Published in: Epigenetics Vol. 14; no. 8; pp. 741 - 750
• Main Authors: Calanca, Naiade, Paschoal, Ana Paula, Munhoz, Érika Prando, Galindo, Layla Testa, Barbosa, Barbara Mitsuyasu, Caldeira, José Roberto Fígaro, Oliveira, Rogério Antonio, Cavalli, Luciane Regina, Rogatto, Silvia Regina, Rainho, Cláudia Aparecida
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03-08-2019; Taylor & Francis Group
• Subjects: Alternative Splicing; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Brief Report; Cell Line, Tumor; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Humans; lncrna; locus-specific epigenetic repression; MCF-7 Cells; rassf1-as1; rassf1a; rassf1c; RNA, Long Noncoding - genetics; Tumor Burden; Tumor Suppressor Proteins - genetics; specific epigenetic repression; DNA methylation; lncRNA; RASSF1C; RASSF1-AS1; RASSF1A
• ISSN: 1559-2294; 1559-2308
• DOI: 10.1080/15592294.2019.1615355

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-2'-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
.