Long Non-Coding RNAs at the Chromosomal Risk Loci Identified by Prostate and Breast Cancer GWAS.
Ontology highlight
ABSTRACT:
SUBMITTER: Janaththani P
PROVIDER: S-EPMC8701176 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:In an attempt to find the correlation of aberrant expression of long intergenic noncoding RNAs (lincRNAs) with cancer, twenty-five samples of breast cancer tissue and respective adjacent normal tissue were studied for the expression of lincRNAs by RNA-seq. Among the 538 lincRNAs studied, 124 lincRNAs were exclusively expressed in cancer adjacent tissues and 62 lincRNAs were exclusively expressed in the cancer tissues. Furthermore, the expression of 134 lincRNAs was higher while 272 lower in breast cancer tissue compared with adjacent tissue. The expression of four selected lincRNAs (BC2, BC4, BC5, and BC8) was validated by semi-quantitative and real-time PCR. It was revealed that expression of lincRNA-BC5 was positively correlated with patients' age, pathological stage, and progesterone receptor concentration, while lincRNA-BC8 was negatively correlated with progesterone receptor expression. Higher expression of lincRNA-BC4 was seen in advanced breast cancer grade. LincRNA-BC2 showed no specific changes in the pathological features studied. Interactions between selected lincRNAs and breast cancer associated proteins were highly suggested by RPIseq based on the specific secondary structure. The results demonstrated that this group of lincRNAs was aberrantly expressed in breast cancer. They might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of breast cancer.
| S-EPMC4118859 | biostudies-literature
Project description:The importance of long non-coding RNAs (lncRNAs) in the pathogenesis of various malignancies has been uncovered over the last few years. Their dysregulation often contributes to or is a result of tumour progression. In prostate cancer, the most common malignancy in men, lncRNAs can promote castration resistance, cell proliferation, invasion, and metastatic spread. Expression patterns of lncRNAs often change during tumour progression; their expression levels may constantly rise (e.g., HOX transcript antisense RNA, HOTAIR), or steadily decrease (e.g., downregulated RNA in cancer, DRAIC). In prostate cancer, lncRNAs likewise have diagnostic (e.g., prostate cancer antigen 3, PCA3), prognostic (e.g., second chromosome locus associated with prostate-1, SChLAP1), and predictive (e.g., metastasis-associated lung adenocarcinoma transcript-1, MALAT-1) functions. Considering their dynamic role in prostate cancer, lncRNAs may also serve as therapeutic targets, helping to prevent development of castration resistance, maintain stable disease, and prohibit metastatic spread.
| S-EPMC5344005 | biostudies-other
Project description:Prostate cancer (PCa) is one of the most frequently diagnosed malignancy. Although there have been many advances in PCa diagnosis and therapy, the concrete mechanism remains unknown. Long non-coding RNAs (lncRNAs) are novel biomarkers associated with PCa, and their dysregulated expression is closely associated with risk stratification, diagnosis and carcinogenesis. Accumulating evidence has suggested that lncRNAs play important roles in prostate tumorigenesis through relevant pathways, such as androgen receptor interaction and PI3K/Akt. The present review systematically summarized the potential clinical utility of lncRNAs and provided a novel guide for their function in PCa.
| S-EPMC7523280 | biostudies-literature
Project description:Breast cancer (BC) is the most common cancer and the leading cause of death in women. Advances in early diagnosis and therapeutic strategies have decreased the mortality of BC and improved the prognosis of patients to some extent. However, the development of drug resistance has limited the success rate of systemic therapies. Long non-coding RNAs (lncRNAs) are involved in drug resistance in BC via various mechanisms, which contribute to a complex regulatory network. In this review, we summarize the latest findings on the mechanisms underlying drug resistance modulated by lncRNAs in BC. In addition, we discuss the potential clinical applications of lncRNAs as targeted molecular therapy against drug resistance in BC.
| S-EPMC7382578 | biostudies-literature
Project description:Osteoporosis, characterized by low bone mineral density (BMD), is the most common complex disease affecting bone and constitutes a major societal health problem. Genome-wide association studies (GWASs) have identified over 1100 associations influencing BMD. It has been shown that perturbations to long non-coding RNAs (lncRNAs) influence BMD and the activities of bone cells; however, the extent to which lncRNAs are involved in the genetic regulation of BMD is unknown. Here, we combined the analysis of allelic imbalance (AI) in human acetabular bone fragments with a transcriptome-wide association study (TWAS) and expression quantitative trait loci (eQTL) colocalization analysis using data from the Genotype-Tissue Expression (GTEx) project to identify lncRNAs potentially responsible for GWAS associations. We identified 27 lncRNAs in bone that are located in proximity to a BMD GWAS association and harbor SNPs demonstrating AI. Using GTEx data we identified an additional 31 lncRNAs whose expression was associated (FDR correction<0.05) with BMD through TWAS and had a colocalizing eQTL (regional colocalization probability (RCP)>0.1). The 58 lncRNAs are located in 43 BMD associations. To further support a causal role for the identified lncRNAs, we show that 23 of the 58 lncRNAs are differentially expressed as a function of osteoblast differentiation. Our approach identifies lncRNAs that are potentially responsible for BMD GWAS associations and suggest that lncRNAs play a role in the genetics of osteoporosis.
2021-11-04 | GSE186922 | GEO
Project description:Genome-wide association studies (GWAS) have proven a fundamental tool to identify common variants associated to complex traits, thus contributing to unveil the genetic components of human disease. Besides, the advent of GWAS contributed to expose unexpected findings that urged to redefine the framework of population genetics. First, loci identified by GWAS had small effect sizes and could only explain a fraction of the predicted heritability of the traits under study. Second, the majority of GWAS hits mapped within non-coding regions (such as intergenic or intronic regions) where new functional RNA species (such as lncRNAs or circRNAs) have started to emerge. Bigger cohorts, meta-analysis and technical improvements in genotyping allowed identification of an increased number of genetic variants associated to coronary artery disease (CAD) and cardiometabolic traits. The challenge remains to infer causal mechanisms by which these variants influence cardiovascular disease development. A tendency to assign potential causal variants preferentially to coding genes close to lead variants contributed to disregard the role of non-coding elements. In recent years, in parallel to an increased knowledge of the non-coding genome, new studies started to characterize disease-associated variants located within non-coding RNA regions. The upcoming of databases integrating single-nucleotide polymorphisms (SNPs) and non-coding RNAs together with novel technologies will hopefully facilitate the discovery of causal non-coding variants associated to disease. This review attempts to summarize the current knowledge of genetic variation within non-coding regions with a focus on long non-coding RNAs that have widespread impact in cardiometabolic diseases.
| S-EPMC6304420 | biostudies-literature
Project description:Recently, large numbers of normal human tissues have been profiled for non-coding RNAs and more than fourteen thousand long intergenic non-coding RNAs (lincRNAs) are found expressed in normal human tissues. The functional roles of these normal lincRNAs (nlincRNAs) in the regulation of protein coding genes in normal and disease biology are yet to be established. Here, we have profiled two RNA-seq datasets including cancer and matched non-neoplastic tissues from 12 individuals from diverse demography for both coding genes and nlincRNAs. We find 130 nlincRNAs significantly regulated in cancer, with 127 regulated in the same direction in the two datasets. Interestingly, according to Illumina Body Map, significant numbers of these nlincRNAs display baseline null expression in normal prostate tissues but are specific to other tissues such as thyroid, kidney, liver and testis. A number of the regulated nlincRNAs share loci with coding genes, which are either co-regulated or oppositely regulated in all cancer samples studied here. For example, in all cancer samples i) the nlincRNA, TCONS_00029157, and a neighboring tumor suppressor factor, SIK1, are both down regulated; ii) several thyroid-specific nlincRNAs in the neighborhood of the thyroid-specific gene TPO, are both up-regulated; and iii) the TCONS_00010581, an isoform of HEIH, is down-regulated while the neighboring EZH2 gene is up-regulated in cancer. Several nlincRNAs from a prostate cancer associated chromosomal locus, 8q24, are up-regulated in cancer along with other known prostate cancer associated genes including PCAT-1, PVT1, and PCAT-92. We observe that there is significant bias towards up-regulation of nlincRNAs with as high as 118 out of 127 up-regulated in cancer, even though regulation of coding genes is skewed towards down-regulation. Considering that all reported cancer associated lincRNAs (clincRNAs) are biased towards up-regulation, we conclude that this bias may be functionally relevant.
| S-EPMC4416928 | biostudies-literature
Project description:Breast cancer represents a major health burden in Europe and North America, as recently published data report breast cancer as the second leading cause of cancer related death in women worldwide. Breast cancer is regarded as a highly heterogeneous disease in terms of clinical course and biological behavior and can be divided into several molecular subtypes, with different prognosis and treatment responses. The discovery of numerous non-coding RNAs has dramatically changed our understanding of cell biology, especially the pathophysiology of cancer. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts >200 nucleotides in length. Several studies have demonstrated their role as key regulators of gene expression, cell biology and carcinogenesis. Deregulated expression levels of lncRNAs have been observed in various types of cancers including breast cancer. lncRNAs are involved in cancer initiation, progression, and metastases. In this review, we summarize the recent literature to highlight the current status of this class of long non-coding lncRNAs in breast cancer.
| S-EPMC5037763 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) have been recently shown to play an important role in gene regulation and normal cellular functions, and disease processes. However, despite the overwhelming number of lncRNAs identified to date, little is known about their role in cancer for vast majority of them. The present study aims to determine whether lncRNAs can serve as prognostic markers in human breast cancer. We interrogated the breast invasive carcinoma dataset of the Cancer Genome Atlas (TCGA) at the cBioPortal consisting of ~ 1,000 cases. Among 2,730 lncRNAs analyzed, 577 lncRNAs had alterations ranging from 1% to 32% frequency, which include mutations, alterations of copy number and RNA expression. We found that deregulation of 11 lncRNAs, primarily due to copy number alteration, is associated with poor overall survival. At RNA expression level, upregulation of 4 lncRNAs (LINC00657, LINC00346, LINC00654 and HCG11) was associated with poor overall survival. A third signature consists of 9 lncRNAs (LINC00705, LINC00310, LINC00704, LINC00574, FAM74A3, UMODL1-AS1, ARRDC1-AS1, HAR1A, and LINC00323) and their upregulation can predict recurrence. Finally, we selected LINC00657 to determine their role in breast cancer, and found that LINC00657 knockout significantly suppresses tumor cell growth and proliferation, suggesting that it plays an oncogenic role. Together, these results highlight the clinical significance of lncRNAs, and thus, these lncRNAs may serve as prognostic markers for breast cancer.
| S-EPMC4991477 | biostudies-literature
Project description:BACKGROUND: Recent analysis of the mouse transcriptional data has revealed the existence of approximately 34,000 messenger-like non-coding RNAs (ml-ncRNAs). Whereas the functional properties of these ml-ncRNAs are beginning to be unravelled, no functional information is available for the large majority of these transcripts. RESULTS: A few ml-ncRNA have been shown to have genomic loci that overlap with microRNA loci, leading us to suspect that a fraction of ml-ncRNA may encode microRNAs. We therefore developed an algorithm (PriMir) for specifically detecting potential microRNA-encoding transcripts in the entire set of 34,030 mouse full-length ml-ncRNAs. In combination with mouse-rat sequence conservation, this algorithm detected 97 (80 of them were novel) strong miRNA-encoding candidates, and for 52 of these we obtained experimental evidence for the existence of their corresponding mature microRNA by microarray and stem-loop RT-PCR. Sequence analysis of the microRNA-encoding RNAs revealed an internal motif, whose presence correlates strongly (R2 = 0.9, P-value = 2.2 x 10(-16)) with the occurrence of stem-loops with characteristics of known pre-miRNAs, indicating the presence of a larger number microRNA-encoding RNAs (from 300 up to 800) in the ml-ncRNAs population. CONCLUSION: Our work highlights a unique group of ml-ncRNAs and offers clues to their functions.
| S-EPMC2410135 | biostudies-literature