Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer

Abstract

Breast cancer (BC) is the most frequently occurring malignancy in women worldwide. Despite the substantial advancement in understanding the molecular mechanisms and management of BC, it remains the leading cause of cancer death in women. One of the main reasons for this obstacle is that we have not been able to find the Achilles heel for the BC as a highly heterogeneous disease. Accumulating evidence has revealed that noncoding RNAs (ncRNAs), play key roles in the development of BC; however, the involving of complex regulatory interactions between the different varieties of ncRNAs in the development of this cancer has been poorly understood. In the recent years, the newly discovered mechanism in the RNA world is “competing endogenous RNA (ceRNA)” which proposes regulatory dialogues between different RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). In the latest BC research, various studies have revealed that dysregulation of several ceRNA networks (ceRNETs) between these ncRNAs has fundamental roles in establishing the hallmarks of BC development. And it is thought that such a discovery could open a new window for a better understanding of the hidden aspects of breast tumors. Besides, it probably can provide new biomarkers and potential efficient therapeutic targets for BC. This review will discuss the existing body of knowledge regarding the key functions of ceRNETs and then highlights the emerging roles of some recently discovered ceRNETs in several hallmarks of BC. Moreover, we propose for the first time the “ceRnome” as a new term in the present article for RNA research.

LncRNA IGFL2‐AS1 functions as a ceRNA in regulating ARPP19 through competitive binding to miR‐802 in gastric cancer

“…Subcellular fractionation assay revealed that IGFL2‐AS1 was located primarily in the cytoplasm, and scarcely in the nucleus in SGC‐7901 or BGC‐823 cells (Figure 3B), suggesting that IGFL2‐AS1 may be involved in posttranscriptional regulation of target genes. LncRNAs can function as competing endogenous RNA (ceRNA) by sponging miRNAs 27,28 . Bioinformatics analysis was performed using the online database RegRNA 2.0 (http://regrna2.mbc.nctu.edu.tw/detection.html) to identify miRNAs that interact with IGFL2‐AS1.…”

“…LncRNAs can function as competing endogenous RNA (ceRNA) by sponging miRNAs. 27,28 Bioinformatics analysis was performed using the online database miR-4656) were predicted to interact with IGFL2-AS1. Luciferase reporter assay was then conducted to verify the interaction between the miRNAs and IGFL2-AS1.…”

Characterization of lncRNA LINC00520 and functional polymorphisms associated with breast cancer susceptibility in Chinese Han population

“…Particularly, adverse rules of miRNAs‐sponging lncRNAs, involved in ceRNA networks (ceRNETs), have been shown in BC . Eades discovered lincRNA‐ROR/miR‐145/ARF6 mRNA networks interacting with metastasis and prognosis in triple‐negative BC in 2015 …”

“…14 Eades discovered lincRNA-ROR/miR-145/ ARF6 mRNA networks interacting with metastasis and prognosis in triple-negative BC in 2015. 15 Long intergenic nonprotein coding RNA 520 (LINC00520) is located at human chromosome 14q22.3. LINC00520, a highly conserved long-chain noncoding RNA with a length of about 20kb, is widely expressed in various tissues.…”

The Butterfly Effect of RNA Alterations on Transcriptomic Equilibrium

“…Although much remains to be discovered about the stoichiometry, subcellular localization, and other factors underpinning the effectiveness of ceRNA regulation, a tremendous body of literature from multiple studies has identified specific miRNA/ceRNA networks that are key players in the development of several cancers. These have been extensively reviewed elsewhere [49][50][51][52].…”