Dysregulation of long non-coding RNA in breast cancer

Long non-coding RNAs (lncRNAs), which occupy nearly 98% of genome, have crucial roles in cancer development, including breast cancer. Breast cancer is a disease with high incidence. Despite of recent progress in understanding the molecular mechanisms and combined therapy strategies, the functions and mechanisms of lncRNAs in breast cancer remains unclear.

Researchers from Zhejiang University review the currently basic knowledge and research approaches of lncRNAs. They also highlight the latest advances of seven classic lncRNAs and three novel lncRNAs in breast cancer, elucidating their mechanisms and possible therapeutic targets. Additionally, association between lncRNA and specific molecular subtype of breast cancer is reported. Lastly, they briefly delineate the potential roles of lncRNAs in clinical applications as biomarkers and treatment targets.

Roles of oncogenic lncRNAs in breast cancer



A. HOTAIR acts as a scaffold by binding the PRC2 complex or LSD1/coREST/REST complex, leading to gene regulation via histone modifications. B. HOTAIR guides the PRC2 complex to epigenetically repress the HoxD10 locus, which reduces miR7 as well. Reduction of miR7 releases inhibition of SETDB1, which promotes the EMT-related pathway. C. MALAT1 negatively controls CD133 transcription via HuR. D. MALAT1 assembles serine/arginine splicing factors (SF) mainly in the nuclear spectacle. Losing MALAT1 leads SR proteins to be abnormally distributed and abnormally phosphorylated, interfering with proper mRNA processing. E. BCAR4 binds with SNIP1 and PNUTS, inducing gene transcription associated with migration. F. BCAR4 could be suppressed by LNA. G. H19 is the origin of miR675. MiR675 could positively feedback to increase H19 expression by the SLUG/E-cadherin pathway. Alternatively, miR675 protects EGFR by degrading two ubiquitin ligase E3s, facilitating cell proliferation and metastasis through the AKT/ERK pathway. H. SRA, as a scaffold, links different complexes to progestin-induced genes when the progestin receptor is not liganded by progestin. I. SRA mediates chromosome organization cooperating with CTCF, P68 and the cohesion complex. J. LINP1 binds Ku80 and DNA-PKcs as a scaffold, contributing to their function in repairing of DNA double strand breaks. This process also includes molecular Ku70. K. LINK-A interacted with both BRK and LRRK2. This complex transfers signal from EGFR:GPNMB heterodimer to nuclear by phosphorylating HIF1α.

Wang J, Ye C, Xiong H, Shen Y, Lu Y, Zhou J, Wang L. (2016) Dysregulation of long non-coding RNA in breast cancer: an overview of mechanism and clinical implication. Oncotarget [Epub ahead of print]. [article]

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