Long Noncoding RNA and Epithelial Mesenchymal Transition in Cancer

Abstract

Epithelial–mesenchymal transition (EMT) is a multistep process that allows epithelial cells to acquire mesenchymal properties. Fundamental in the early stages of embryonic development, this process is aberrantly activated in aggressive cancerous cells to gain motility and invasion capacity, thus promoting metastatic phenotypes. For this reason, EMT is a central topic in cancer research and its regulation by a plethora of mechanisms has been reported. Recently, genomic sequencing and functional genomic studies deepened our knowledge on the fundamental regulatory role of noncoding DNA. A large part of the genome is transcribed in an impressive number of noncoding RNAs. Among these, long noncoding RNAs (lncRNAs) have been reported to control several biological processes affecting gene expression at multiple levels from transcription to protein localization and stability. Up to now, more than 8000 lncRNAs were discovered as selectively expressed in cancer cells. Their elevated number and high expression specificity candidate these molecules as a valuable source of biomarkers and potential therapeutic targets. Rising evidence currently highlights a relevant function of lncRNAs on EMT regulation defining a new layer of involvement of these molecules in cancer biology. In this review we aim to summarize the findings on the role of lncRNAs on EMT regulation and to discuss their prospective potential value as biomarkers and therapeutic targets in cancer.

Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT

“…Even though loss of E-cadherin is considered a hallmark event of EMT, many other signals and cellular events are required to activate this process. Up to recent years, lncR-NAs has emerged as important regulators of several biological processes (15). LINC-ROR is highly expressed in ESC and its implicated in the maintenance of pluripotency since act as sponge of microRNA that repress the translation of pluripotency genes, ensuring the undifferentiated state.…”

“…Activation of EMT occurs in response to various factors and signals. Different reports tend to focus on the study of long non coding RNA (lncRNA) as fundamental regulators of EMT in cancer stem cells and PSC (15). Based on this background, our next step consisted on evaluating the expression of LINC-ROR and MALAT1, two lncRNAs considered as EMT regulators, during E-cadherin downregulation.…”

EMT Factors and Metabolic Pathways in Cancer

“…Long non-coding RNAs (lncRNAs), i.e., non-coding RNAs of >200 nucleotides in length, are also involved in a plethora of biological processes, including EMT (187,188). Hundreds of lncRNAs are deregulated during EMT (187), either promoting (189)(190)(191)(192) or inhibiting it (193)(194)(195)(196).…”

“…Our understanding of the roles of lncRNAs is rapidly advancing. Expression levels of disparate lncRNAs are being investigated as clinical biomarkers of cancer diagnosis and prognosis (188) and could harbor clinical opportunities for intervention in EMT. Ofcourse, the research on the role of lncRNAs on metabolism is expanding (204) but currently there is not a lot of studies (205) linking them with cancer cell metabolism and specifically the ones that are related with the EMT process.…”

Transcriptomic and ChIP-seq Integrative Analysis Reveals Important Roles of Epigenetically Regulated lncRNAs in Placental Development in Meishan Pigs

“…Long non-coding RNAs (lncRNAs) are known to be larger than 200 nt with little or no coding potential [12,13]. They play a diverse role in biological processes, including transcriptional and post-transcriptional regulation, as well as chromatin remodeling [14][15][16][17][18][19].…”