Characteristics Of lncRNAs Research Articles

Identification and characterization of long non-coding RNAs in mammary gland tissues of Chinese Holstein cows.

LncRNAs (Long non-coding RNA) is an RNA molecule with a length of more than 200bp. LncRNAs can directly act on mRNA, thus affecting the expression of downstream target genes and proteins, and widely participate in many important physiological and pathological regulation processes of the body. In this study, RNA-Seq was performed to detect lncRNAs from mammary gland tissues of three Chinese Holstein cows, including three cows at 7 d before calving and the same three cows at 30 d postpartum (early lactation stage). A total of 1,905 novel lncRNAs were detected, 57.3% of the predicted lncRNAs are ≥ 500bp and 612 lncRNAs are intronic lncRNAs. The exon number of lncRNAs ranged from 2 to 10. A total of 96 lncRNAs were significantly differentially expressed between two stages, of which 47 were upregulated and 49 were downregulated. Pathway analysis found that target genes were mainly concentrated on the ECM-receptor interaction, Jak-STAT signaling pathway, PI3K-Akt signaling pathway, and TGF-beta signaling pathway. This study revealed the expression profile and characteristics of lncRNAs in the mammary gland tissues of Holstein cows at non-lactation and early lactation periods, and provided a basis for studying the functions of lncRNAs in Holstein cows during different lactation periods.

Identification and Classification of Long Non-Coding RNAs in the Mammary Gland of the Holstein Cow.

The mammary glands, responsible for milk secretion, are regulated at a local level by various hormones, growth factors, non-coding RNAs, and other elements. Recent research has discovered the presence of lncRNAs in these glands, with suggestions that they may be essential for the maintenance and function of mammary glands. Besides directly controlling the gene and protein expression, lncRNAs are believed to play a significant part in numerous physiological and pathological processes. This study focused on examining the mammary gland tissues of Chinese Holstein cows, to identify and categorize long non-coding RNAs (lncRNAs). The research intended to distinguish lncRNAs in the mammary tissues of Holstein cows and contrast them between lactation and non-lactation periods. In this study, mammary gland tissues were sampled from three Holstein cows in early lactation (n = 3, 30 days postpartum) and non-lactation (n = 3, 315 days postpartum) on a large dairy farm in Jiangsu province. Mammary tissue samples were collected during early lactation and again during non-lactation. In total, we detected 1905 lncRNAs, with 57.3% being 500 bp and 612 intronic lncRNAs. The exon count for lncRNAs varied from 2 to 10. It was observed that 96 lncRNA expressions markedly differed between the two stages, with 83 genes being upregulated and 53 downregulated. Enrichment analysis results revealed that Gene Ontology (GO) analysis was primarily abundant in cellular processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that target genes were predominantly abundant in metabolic pathways, fatty acid biosynthesis, the immune system, and glycosphingolipid biosynthesis. This study analyzed the expression profile and characteristics of lncRNAs in the mammary gland tissues of Holstein cows during both lactation and non-lactation stages, forming a foundation for further investigation into the functional roles of lncRNAs in Holstein cows throughout lactation.

A novel hypoxia-stimulated lncRNA HIF1A-AS3 binds with YBX1 to promote ovarian cancer tumorigenesis by suppressing p21 and AJAP1 transcription.

Hypoxia is characteristic of the ovarian tumor (OC) microenvironment and profoundly affects tumorigenesis and therapeutic response. Long noncoding RNAs (lncRNAs) play various roles in tumor progression; however, the characteristics of lncRNAs in pathological responses of the OC microenvironment are not entirely understood. Through high-throughput sequencing, lncRNA expression in hypoxia (1% O2 ) and normoxia (21% O2 ) SKOV3 cells was explored and analyzed. The 5'- and 3'-rapid amplification of complementary DNA ends was used to detect the full length of the novel HIF1A-AS3 transcript. Real-time quantitative polymerase chain reaction was used to assess HIF1A-AS3 expression in OC cells and tissues. In vitro and in vivo evaluations of the biological functions of hypoxic HIF1A-AS3 were conducted. To clarify the underlying mechanisms of HIF1A-AS3 in hypoxic OC, a dual-luciferase assay, chromatin immunoprecipitation, RNA pull-down, RNA immunoprecipitation, and RNA-sequencing were used. We used high-throughput sequencing to investigate a novel lncRNA, HIF1A-AS3, as a hypoxic candidate significantly elevated in OC cells/tissues. HIF1A-AS3 was predominantly localized in the nucleus and promotedin vitro and in vivo OC growth and tumorigenesis. Hypoxia-inducible factor 1α bound to hypoxia response elements in the HIF1A-AS3 promoter region and stimulated its expression in hypoxia. Under hypoxia, HIF1A-AS3 directly integrated withY-Box binding protein 1 and inhibited its ability to bind to the promoters of p21 and AJAP1 to repress their transcriptional activity, thereby promoting hypoxic OC progression. Our results revealed the crucial role and mechanism of the novel hypoxic HIF1A-AS3 in the oncogenesis of OC. The novel HIF1A-AS3 could be a crucial biomarker and therapeutic target for future OC treatments.

Molecular and cellular functions of long non-coding RNAs in prostate and breast cancer.

Long noncoding RNAs (lncRNAs) are defined as noncoding RNA transcripts with a length greater than 200 nucleotides. Research over the last decade has made great strides in our understanding of lncRNAs, especially in the biology of their role in cancer. In this article, we will briefly discuss the biogenesis and characteristics of lncRNAs, then review their molecular and cellular functions in cancer by using prostate and breast cancer as examples. LncRNAs are abundant, diverse, and evolutionarily, less conserved than protein-coding genes. They are often expressed in a tumor and cell-specific manner. As a key epigenetic factor, lncRNAs can use a wide variety of molecular mechanisms to regulate gene expression at each step of the genetic information flow pathway. LncRNAs display widespread effects on cell behavior, tumor growth, and metastasis. They act intracellularly and extracellularly in an autocrine, paracrine and endocrine fashion. Increased understanding of lncRNA's role in cancer has facilitated the development of novel biomarkers for cancer diagnosis, led to greater understanding of cancer prognosis, enabled better prediction of therapeutic responses, and promoted identification of potential targets for cancer therapy.

ICLRBBN: a tool for accurate prediction of potential lncRNA disease associations

Growing evidence has elucidated that long non-coding RNAs (lncRNAs) are involved in a variety of complex diseases in human bodies. In recent years, it has become a hot topic to develop effective computational models to identify potential lncRNA-disease associations. In this article, a novel method called ICLRBBN (Internal Confidence-Based Local Radial Basis Biological Network) is proposed to detect potential lncRNA-disease associations by adopting an internal confidence-based radial basis biological network. In ICLRBBN, a novel internal confidence-based collaborative filtering recommendation algorithm was designed first to mine hidden features between lncRNAs and diseases, which guarantees that ICLRBBN can be more effectively applied to predict new diseases. Then, a unique three-layer local radial basis function network consisting of diseases and lncRNAs was constructed, based on which the association probability between diseases and lncRNAs was calculated by combining different characteristics of lncRNAs with local information of diseases. Finally, we compared ICLRBBN with 6 state-of-the-art methods based on two different validation frameworks. Simulation results showed that area under the receiver operating characteristic curve (AUC) values achieved by ICLRBBN outperformed all competing methods. Furthermore, case studies illustrated that ICLRBBN has a promising future as a powerful tool in the practical application of lncRNA-disease association prediction. A web service for prediction of potential lncRNA-disease associations is available at http://leelab2997.cn/.

Predicting the interaction biomolecule types for lncRNA: an ensemble deep learning approach.

Long noncoding RNAs (lncRNAs) play significant roles in various physiological and pathological processes via their interactions with biomolecules like DNA, RNA and protein. The existing in silico methods used for predicting the functions of lncRNA mainly rely on calculating the similarity of lncRNA or investigating whether an lncRNA can interact with a specific biomolecule or disease. In this work, we explored the functions of lncRNA from a different perspective: we presented a tool for predicting the interaction biomolecule type for a given lncRNA. For this purpose, we first investigated the main molecular mechanisms of the interactions of lncRNA-RNA, lncRNA-protein and lncRNA-DNA. Then, we developed an ensemble deep learning model: lncIBTP (lncRNA Interaction Biomolecule Type Prediction). This model predicted the interactions between lncRNA and different types of biomolecules. On the 5-fold cross-validation, the lncIBTP achieves average values of 0.7042 in accuracy, 0.7903 and 0.6421 in macro-average area under receiver operating characteristic curve and precision-recall curve, respectively, which illustrates the model effectiveness. Besides, based on the analysis of the collected published data and prediction results, we hypothesized that the characteristics of lncRNAs that interacted with DNA may be different from those that interacted with only RNA.

Systematic identification of long intergenic non-coding RNAs expressed in bovine oocytes

BackgroundLong non-coding RNAs (lncRNAs) are key regulators of diverse cellular processes. Although a number of studies have reported the identification of bovine lncRNAs across many tissues, very little is known about the identity and characteristics of lncRNAs in bovine oocytes.MethodsA bovine oocyte cDNA library was constructed and sequenced using the Illumina HiSeq 2000 sequencing system. The oocyte transcriptome was constructed using the ab initio assembly software Scripture and Cufflinks. The assembled transcripts were categorized to identify the novel intergenic transcripts, and the coding potential of these novel transcripts was assessed using CPAT and PhyloCSF. The resulting candidate long intergenic non-coding RNAs (lincRNAs) transcripts were further evaluated to determine if any of them contain any known protein coding domains in the Pfam database. RT-PCR was used to analyze the expression of oocyte-expressed lincRNAs in various bovine tissues.ResultsA total of 85 million raw reads were generated from sequencing of the bovine oocyte library. Transcriptome reconstruction resulted in the assembly of a total of 42,396 transcripts from 37,678 genomic loci. Analysis of the assembled transcripts using the step-wide pipeline resulted in the identification of 1535 oocyte lincRNAs corresponding to 1183 putative non-coding genes. A comparison of the oocyte lincRNAs with the lncRNAs reported in other bovine tissues indicated that 970 of the 1535 oocyte lincRNAs appear to be unique to bovine oocytes. RT-PCR analysis of 5 selected lincRNAs showed either specific or predominant expression of 4 lincRNAs in the fetal ovary. Functional prediction of the oocyte-expressed lincRNAs suggested their involvement in oogenesis through regulating their neighboring protein-coding genes.ConclusionsThis study provides a starting point for future research aimed at understanding the roles of lncRNAs in controlling oocyte development and early embryogenesis in cattle.

LncRNAs in ocular neovascularizations.

The prevalence of eye diseases worldwide is dramatically increasing and represents a major concern in underdeveloped and developed regions. Ocular diseases, previously associated with a higher depression risk, also impose a substantial economic burden on affected families, thus early detection and/or accurate treatment in order to avoid and prevent blindness should be emphasized. Ocular neovascularization (NV), the leading cause of blindness in a variety of eye diseases, is a pathologic process characterized by the formation, proliferation and infiltration of anomalous, tiny and leaky fragile blood vessels within the eye. Genetics have been suspected to play an important role in the occurrence of eye diseases, with the detection of a numbers of specific gene mutations. Long non-coding RNA (lncRNAs) are novel class of regulatory molecules previously associated with various biological processes and diseases, however the nature of the relation and pathways by which they might contribute to the development of corneal, choroidal and retinal NV have not yet been completely elucidated. In this review, we focus on the regulation and characteristics of lncRNAs, summarize results from ocular NV-related studies and discuss the implication of lncRNAs in ocular NV development.

Crosstalk between long non-coding RNAs and Wnt/β-catenin signalling in cancer.

Long non‐coding RNAs (lncRNAs) are non‐protein‐coding transcripts in the human genome which perform crucial functions in diverse biological processes. The abnormal expression of some lncRNAs has been found in tumorigenesis, development and therapy resistance of cancers. They may act as oncogenes or tumour suppressors and can be used as diagnostic or prognostic markers, prompting their therapeutic potentials in cancer treatments. Studies have indicated that many lncRNAs are involved in the regulation of several signal pathways, including Wnt/β‐catenin signalling pathway, which has been reported to play a significant role in regulating embryogenesis, cell proliferation and controlling tumour biology. Emerging evidences have suggested that lncRNAs can interact with several components of the Wnt/β‐catenin signalling pathway to regulate the expression of Wnt target genes in cancer. Moreover, the expression of lncRNAs can also be influenced by the pathway. Nevertheless, Wnt/β‐catenin signalling pathway‐related lncRNAs and their interactions in cancer are not systematically analysed before. Considering these, this review emphasized the associations between lncRNAs and Wnt/β‐catenin signalling pathway in cancer initiation, progression and their therapeutic influence. We also provided an overview on characteristics of lncRNAs and Wnt/β‐catenin signalling pathway and discussed their functions in tumour biology. Finally, targeting lncRNAs or/and molecules associated with the Wnt/β‐catenin signalling pathway may be a feasible therapeutic method in the future.

Abstract 570: Characteristics of Long Non-coding RNAs in the Brown Norway Rat and Alterations in the Dahl Salt-Sensitive Rat

Long non-coding RNAs (lncRNAs) are emerging as important mediators of genomic regulation. lncRNAs, however, remain poorly characterized in the rat model organism, which is widely used in hypertension research. Using poly(A)-independent and strand-specific RNA-seq, we identified approximately 1,500 to 1,800 lncRNAs expressed in each of the following tissues of Brown Norway rats: the renal cortex, renal outer medulla, liver, cardiac left ventricle, adrenal gland, and hypothalamus. Expression patterns and the binding of histone H3K4me3 to promoter regions were confirmed for several of the identified lncRNAs. Patterns of rat lncRNA expression appeared to be more tissue-specific than mRNA. Rat lncRNAs, on average, had similar lengths to mRNA but substantially fewer exons. The median abundance of rat lncRNAs was approximately 40% of that of mRNA. Approximately 28% of the lncRNAs identified in the renal outer medulla appeared to lack a poly(A) tail. Differential expression of 74 lncRNAs was detected in the renal outer medulla between Dahl salt-sensitive SS rats and salt-insensitive, congenic SS.13BN26 rats fed a high-salt diet. Two of the differentially expressed lncRNAs, which were confirmed, were located within the substituted congenic region. The study identified genome-wide characteristics of lncRNAs in the rat model and suggested a role of lncRNAs in hypertension.