Keeping abreast with long non-coding RNAs in mammary gland development and breast cancer

Abstract

The majority of the human genome is transcribed, even though only 2% of transcripts encode proteins. Non-coding transcripts were originally dismissed as evolutionary junk or transcriptional noise, but with the development of whole genome technologies, these non-coding RNAs (ncRNAs) are emerging as molecules with vital roles in regulating gene expression. While shorter ncRNAs have been extensively studied, the functional roles of long ncRNAs (lncRNAs) are still being elucidated. Studies over the last decade show that lncRNAs are emerging as new players in a number of diseases including cancer. Potential roles in both oncogenic and tumor suppressive pathways in cancer have been elucidated, but the biological functions of the majority of lncRNAs remain to be identified. Accumulated data are identifying the molecular mechanisms by which lncRNA mediates both structural and functional roles. LncRNA can regulate gene expression at both transcriptional and post-transcriptional levels, including splicing and regulating mRNA processing, transport, and translation. Much current research is aimed at elucidating the function of lncRNAs in breast cancer and mammary gland development, and at identifying the cellular processes influenced by lncRNAs. In this paper we review current knowledge of lncRNAs contributing to these processes and present lncRNA as a new paradigm in breast cancer development.

Noncoding RNAs in breast cancer

“…Here we provide a concise review of the roles of representative lncRNAs in breast tumorigenesis. Comprehensive reviews of lncRNAs in breast cancer are available elsewhere [172][173][174][175].…”

“…HOTAIR is an antisense RNA transcribed from the HOXC locus and acts in trans to repress the expression of the HOXD locus [174]. HOTAIR is an RNA scaffold, and the 5 0 and 3 0 domains of HOTAIR are involved in recruiting two critical epigenetic protein complexes, Polycomb Repressive Complex 2 (PRC2) and the LSD1-CoREST-REST H3K4 demethylase complex, to regulate gene expression [177].…”

“…Recently, ingestion of plants bioengineered to produce human cancer-related miRNAs was reported to be a compelling approach for cancer chemoprevention [247]. Although lncRNAs are critical in breast cancer progression and metastasis, therapeutic application is still challenging owing to technical hurdles [174], and more investigation of lncRNAs is necessary.…”

LncRNAs and cancer

“…LcnRNAs may upregulate or downregulate gene expression both transcriptionally and post-transcriptionally. LncRNAs exert a key role in numerous cellular processes, including cell growth, apoptosis and carcinogenesis (3,4) and thus, they are implicated in the progression of various types of human cancer (5). In the present review, the most important and well-known lncRNAs in cancers are discussed and their known and possible molecular functions are outlined briefly, as well as their potential application as therapeutic targets or biomarkers.…”

Non-Coding RNA Roles in Ruminant Mammary Gland Development and Lactation

“…[13,14]). Emerging studies now suggest that non-coding RNAs (ncRNAs) are key regulators of mammary gland development and lactation processes [15][16][17]. The results from the ENCODE (ENCyclopedia of DNA elements) project [18,19] indicate that only a small portion of the genome, about 1.5%, codes for proteins while most of the genome is transcribed into non-coding regulatory elements or ncRNA.…”