Dataset Information

'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. LINKED ARTICLES:This article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.

SUBMITTER: Ong MS

PROVIDER: S-EPMC5727316 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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'Lnc'-ing Wnt in female reproductive cancers: therapeutic potential of long non-coding RNAs in Wnt signalling.

Ong Mei S MS Cai Wanpei W Yuan Yi Y Leong Hin C HC Tan Tuan Z TZ Mohammad Asad A You Ming L ML Arfuso Frank F Goh Boon C BC Warrier Sudha S Sethi Gautam G Tolwinski Nicholas S NS Lobie Peter E PE Yap Celestial T CT Hooi Shing C SC Huang Ruby Y RY Kumar Alan P AP

British journal of pharmacology 20170823 24

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 ...[more]

PMID: 28736855

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Project description:Long non-coding RNAs (lncRNAs) participate in various biological processed involved in tumorigenesis, metastasis and proliferation. The aim of the present study was to identify candidate long non-coding RNAs (lncRNAs) involved in sentinel lymph node (SLN) metastasis in breast cancer. Specimens of SLNs were collected from patients with SLN metastasis via punch biopsy. Total RNA was extracted and RNA sequencing (RNA-seq) was conducted. Differential expression profiles of mRNAs and lncRNAs were obtained via bioinformatics analysis, and Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on differentially expressed mRNAs. The expression levels of lncRNAs were analyzed via reverse transcription-quantitative PCR (RT-qPCR), and the regulation network of the lncRNAs to downstream microRNAs (miRs) and mRNAs was predicted. Based on RNA-seq results, six differentially expressed candidate lncRNAs were identified in patients with and without SLN metastasis: lnc-ANGPTL1-3:3, lnc-GJA10-12:1, lnc-ACAN-2:1, lnc-ZPBP2-4:1, lnc-GATA3-16:1 and lnc-ACOX3-5:1. KEGG and GO analysis identified that the mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways were the most enriched pathways. After RT-qPCR analysis, lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 exhibited expression patterns that were consistent with those from RNA-seq. Moreover, receiver operating characteristic curve analysis demonstrated that lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 expression levels had high sensitivity and specificity in the diagnosis of SLN metastasis, and that their expression levels were upregulated in patients with axillary lymph node metastasis. Further analysis revealed that lnc-GJA10-12:1 and lnc-ANGPTL1-3:3 were commonly involved in regulating the miR-302 family, including miR-302d-3p and miR-302c-3p, which together targeted AKT1. Additionally, lnc-ANGPTL1-3:3 was predicted to target miR-520b to regulate MAP3K2 expression. lnc-GJA10-12:1 was also predicted to target miR-34a-5p to regulate MAP2K1 and MAP3K9 expression levels, as well as miR-449a to regulate MAP2K1 expression. The results of the present study suggested that lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 may potentially serve a role in SLN metastasis of breast cancer by regulating the PI3K/Akt and MAPK signaling pathways via targeting the miR-302 family, miR-520a-3p, miR-34a-5p and miR-449a. Thus, lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 in SLN may serve as potential markers of breast cancer metastasis.

Dataset Information

'Lnc'-ing Wnt in female reproductive cancers: therapeutic potential of long non-coding RNAs in Wnt signalling.

Publications

'Lnc'-ing Wnt in female reproductive cancers: therapeutic potential of long non-coding RNAs in Wnt signalling.

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