%0 Journal Article
%T miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer
%A Katarzyna Augoff
%A Brian McCue
%A Edward F Plow
%A Khalid Sossey-Alaoui
%J Molecular Cancer
%D 2012
%I BioMed Central
%R 10.1186/1476-4598-11-5
%X In the present report, we identify promoter hypermethylation as one of the major mechanisms for silencing miR-31 in breast cancer, and in the triple-negative breast cancer (TNBC) cell lines of basal subtype, in particular. miR-31 maps to the intronic sequence of a novel long non-coding (lnc)RNA, LOC554202 and the regulation of its transcriptional activity is under control of LOC554202. Both miR-31 and the host gene LOC554202 are down-regulated in the TNBC cell lines of basal subtype and over-expressed in the luminal counterparts. Treatment of the TNBC cell lines with either a de-methylating agent alone or in combination with a de-acetylating agent resulted in a significant increase of both miR-31 and its host gene, suggesting an epigenetic mechanism for the silencing of these two genes by promoter hypermethylation. Finally, both methylation-specific PCR and sequencing of bisulfite-converted DNA demonstrated that the LOC554202 promoter-associated CpG island is heavily methylated in the TNBC cell lines and hypomethylated in the luminal subtypes.Loss of miR-31 expression in TNBC cell lines is attributed to hypermethylation of its promoter-associated CpG island. Together, our results provide the initial evidence for a mechanism by which miR-31, an important determinant of the invasion metastasis cascade, is regulated in breast cancer.Metastasis is responsible for ~90% of deaths in patients with solid tumors [1-4], including those originating in the breast [5-7]. Metastasis has always been portrayed as the ultimate step of the progressing breast cancers. Recent evidence, however, indicates that about a third of women diagnosed with small asymptomatic breast tumors (~4 mm) already harbor disseminated BC cells in their bone marrow [8]. Moreover, these micrometastases can remain dormant for years before reemerging as incurable secondary tumors and surprisingly insensitive to adjuvant chemotherapies that were originally effective against the primary tumor [9,10]. Adding to t
%K miR-31
%K LOC554202
%K Triple-negative breast cancer
%K lncRNA
%K CpG hypermethylation
%K Invasion-metastasis cascade
%U http://www.molecular-cancer.com/content/11/1/5