‘Lnc’‐ing Wnt in female reproductive cancers: therapeutic potential of long non‐coding RNAs in Wnt signalling

Abstract

Recent discoveries in the non-coding genome have challenged the original central dogma of molecular biology, as non-coding RNAs and related processes have been found to be important in regulating gene expression. MicroRNAs and long non-coding RNAs (lncRNAs) are among those that have gained attention recently in human diseases, including cancer, with the involvement of many more non-coding RNAs (ncRNAs) waiting to be discovered. ncRNAs are a group of ribonucleic acids transcribed from regions of the human genome, which do not become translated into proteins, despite having essential roles in cellular physiology. Deregulation of ncRNA expression and function has been observed in cancer pathogenesis. Recently, the roles of a group of ncRNA known as lncRNA have gained attention in cancer, with increasing reports of their oncogenic involvement. Female reproductive cancers remain a leading cause of death in the female population, accounting for almost a third of all female cancer deaths in 2016. The Wnt signalling pathway is one of the most important oncogenic signalling pathways which is hyperactivated in cancers, including female reproductive cancers. The extension of ncRNA research into their mechanistic roles in human cancers has also led to novel reported roles of ncRNAs in the Wnt pathway and Wnt-mediated oncogenesis. This review aims to provide a critical summary of the respective roles and cellular functions of Wnt-associated lncRNAs in female reproductive cancers and explores the potential of circulating cell-free lncRNAs as diagnostic markers and lncRNAs as therapeutic targets. LGR5, leucine-rich repeat-containing G-protein coupled receptor 5; lncRNA, long non-coding RNA; LRP, lipoprotein receptor-related protein; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; miRNA, microRNA; NBAT1, neuroblastoma-associated transcript 1; ncRNA, non-coding RNAs; NEAT1, nuclear-enriched abundant transcript 1; NGS, next-generation sequencing; PCA3, prostate cancer antigen 3; PCDH10, protocadherin 10; PCP, Wnt/planar cell polarity; PCR2, polycomb repressive 2; Pinc, pregnancy-induced non-coding RNA; RNAi, RNA interference; shRNA, short hairpin RNAs; TCF, transcription factors T cell factor; UCA1, urothelial carcinoma-associated 1 LINKED ARTICLES

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…This review is not comprehensive with respect to lncRNAs in endocrine-related cancers, but summarizes representative lncRNAs that are bestcharacterized ( Table 2 and described below). Examples of recent reviews of lncRNAs include roles in: female reproductive cancers (Ong, et al 2017), BCa (Malih, et al 2015;Miano, et al 2016;Niknafs, et al 2016;Venkatesh et al 2015;Warburton and Boone 2017), prostate cancer (PCa) (Alahari, et al 2016;, and thyroid cancer (Murugan, et al 2017).…”

“…MALAT1 is considered oncogenic and it upregulates the Wnt/β-catenin pathway (Ong et al 2017). Capture hybridization analysis of RNA targets (CHART) identified MALAT1 genomic binding sites to be at actively transcribed loci (reviewed in ) .…”

lncRNA DLEU1 contributes to tumorigenesis and development of endometrial carcinoma by targeting mTOR

“…lncRNAs are different from mRNAs, which are a group of ribonucleic acids more than 200 nucleotides and challenge the classical central dogma of molecular biology. They involve in processes including proliferation, invasion, migration, and others features of tumors through epigenetic, transcriptional, and post‐transcriptional routes such as modifying histones, interfering with the transcription of the target protein and binding to the protein into a nucleic acid protein complex, despite they cannot be translated to proteins …”

WNT signalling: mechanisms and therapeutic opportunities

“…Recent advances in understanding the non‐coding genome pinpoint a possible role of long noncoding RNA (lncRNA) as a potential target for therapy and/or a means of diagnosing disease. In this context, Alan Prem Kumar and co‐workers summarize what is known about WNT‐associated lncRNAs in female reproductive tract cancers (Ong et al ., ). While a lot of emphasis is on the importance of WNT/β‐catenin/dependent signalling and targeting it in oncology, Janovská and Bryja () demonstrate that in chronic lymphocytic leukaemia and related lymphomas, the β‐catenin‐independent planar cell polarity signalling has a crucial role.…”