The roles of long noncoding RNAs in breast cancer metastasis

Abstract

Breast cancer is the most significant threat to female health. Breast cancer metastasis is the major cause of mortality in breast cancer patients. To fully unravel the molecular mechanisms that underlie the breast cancer cell metastasis is critical for developing strategies to improve survival and prognosis in breast cancer patients. Recent studies have revealed that the long noncoding RNAs (lncRNAs) are involved in breast cancer metastasis through a variety of molecule mechanisms, though the precise functional details of these lncRNAs are yet to be clarified. In the present review, we focus on the functions of lncRNAs in breast cancer invasion and metastasis, with particular emphasis on the functional properties, the regulatory factors, the therapeutic promise, as well as the future challenges in studying these lncRNA.

Fig. 1. The classification of lncRNAs based on their locations of transcripts from genome.

LncRNAs are divided into six groups, i.e., sense, antisense, intronic, bidirectional, intergenic, and enhancer RNAs.

Fig. 2. Functional mechanisms of lncRNAs at transcriptional levels.

a LncRNAs act as decoys titrating away transcription factors and other proteins away from chromatin. b LncRNAs act as guides recruiting chromatin-modifying enzymes to target genes. c LncRNAs act as scaffolds for RNA-binding proteins to recruit chromatin-modifying complexes. In all cases, the binding of the enzymes or the recruiting factors are shown. d LncRNAs act as enhancer RNAs stabilizing looping and recruitment of transcriptional regulators, cofactors, and RNA Pol II, further increasing transcription of the associated gene.

Fig. 3. Functional mechanisms of lncRNAs at posttranscriptional levels.

a LncRNAs change the splicing pattern of the pre-mRNA by regulating phosphorylation forms of the serine/arginine splicing factors. b LncRNAs stabilize mRNAs by forming RNA duplex, thereby preventing degradation. c LncRNAs regulate protein translation through recruiting the translation-related protein complex. d LncRNAs promote the degradation of proteins through recruiting the ubiquitin ligase.

Fig. 4. Functional mechanisms of lncRNAs at epigenetic levels.

a LncRNAs regulate histone modifications or chromatin remodeling by interacting with PRCs or other chromatin-modifying proteins. b LncRNAs regulate DNA methylation in the promoter region of a downstream gene through inhibiting DNA methyltransferase recruitment.

Fig. 5. LncRNA-related signaling pathways in breast cancer metastasis.

Aberrantly expression of lncRNA exerts an important impact on breast cancer metastasis by interacting with the TGF-β, STAT3, NF-κB, Hippo, EGF, Hippo, p53, and PI3K/AKT pathways.