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7,944 result(s) for "lncRNAs"
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The Functions and Unique Features of LncRNAs in Cancer Development and Tumorigenesis
Over the past decades, research on cancer biology has focused on the involvement of protein-coding genes in cancer development. Long noncoding RNAs (lncRNAs), which are transcripts longer than 200 nucleotides that lack protein-coding potential, are an important class of RNA molecules that are involved in a variety of biological functions. Although the functions of a majority of lncRNAs have yet to be clarified, some lncRNAs have been shown to be associated with human diseases such as cancer. LncRNAs have been shown to contribute to many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein and RNA. Here we describe the literature regarding the biogenesis and features of lncRNAs. We also present an overview of the current knowledge regarding the roles of lncRNAs in cancer from the view of various aspects of cellular homeostasis, including proliferation, survival, migration and genomic stability. Furthermore, we discuss the methodologies used to identify the function of lncRNAs in cancer development and tumorigenesis. Better understanding of the molecular mechanisms involving lncRNA functions in cancer is critical for the development of diagnostic and therapeutic strategies against tumorigenesis.
Human Long Noncoding RNA Interactome: Detection, Characterization and Function
The application of a new generation of sequencing techniques has revealed that most of the genome has already been transcribed. However, only a small part of the genome codes proteins. The rest of the genome \"dark matter” belongs to divergent groups of non-coding RNA (ncRNA), that is not translated into proteins. There are two groups of ncRNAs, which include small and long non-coding RNAs (sncRNA and lncRNA respectively). Over the last decade, there has been an increased interest in lncRNAs and their interaction with cellular components. In this review, we presented the newest information about the human lncRNA interactome. The term lncRNA interactome refers to cellular biomolecules, such as nucleic acids, proteins, and peptides that interact with lncRNA. The lncRNA interactome was characterized in the last decade, however, understanding what role the biomolecules associated with lncRNA play and the nature of these interactions will allow us to better understand lncRNA's biological functions in the cell. We also describe a set of methods currently used for the detection of lncRNA interactome components and the analysis of their interactions. We think that such a holistic and integrated analysis of the lncRNA interactome will help to better understand its potential role in the development of organisms and cancers.
A novel autophagy‐related lncRNA prognostic risk model for breast cancer
Long non‐coding RNAs (lncRNAs) are well known as crucial regulators to breast cancer development and are implicated in controlling autophagy. LncRNAs are also emerging as valuable prognostic factors for breast cancer patients. It is critical to identify autophagy‐related lncRNAs with prognostic value in breast cancer. In this study, we identified autophagy‐related lncRNAs in breast cancer by constructing a co‐expression network of autophagy‐related mRNAs‐lncRNAs from The Cancer Genome Atlas (TCGA). We evaluated the prognostic value of these autophagy‐related lncRNAs by univariate and multivariate Cox proportional hazards analyses and eventually obtained a prognostic risk model consisting of 11 autophagy‐related lncRNAs (U62317.4, LINC01016, LINC02166, C6orf99, LINC00992, BAIAP2‐DT, AC245297.3, AC090912.1, Z68871.1, LINC00578 and LINC01871). The risk model was further validated as a novel independent prognostic factor for breast cancer patients based on the calculated risk score by Kaplan‐Meier analysis, univariate and multivariate Cox regression analyses and time‐dependent receiver operating characteristic (ROC) curve analysis. Moreover, based on the risk model, the low‐risk and high‐risk groups displayed different autophagy and oncogenic statues by principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation. Taken together, these findings suggested that the risk model of the 11 autophagy‐related lncRNAs has significant prognostic value for breast cancer and might be autophagy‐related therapeutic targets in clinical practice.
Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility
Background Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate a host of crucial cellular processes like proliferation, differentiation and apoptosis by regulating gene expression. While small noncoding RNAs (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting RNAs have been extensively studied in male germ cell development, the role of lncRNAs in spermatogenesis remains largely unknown. Objective In this article, we have reviewed the biology and role of lncRNAs in spermatogenesis along with the tools available for data analysis. Results and conclusions Till date, three microarray and four RNA-seq studies have been undertaken to identify lncRNAs in mouse testes or germ cells. These studies were done on pre-natal, post-natal, adult testis, and different germ cells to identify lncRNAs regulating spermatogenesis. In case of humans, five RNA-seq studies on different germ cell populations, including two on sperm, were undertaken. We compared three studies on human germ cells to identify common lncRNAs and found 15 lncRNAs (LINC00635, LINC00521, LINC00174, LINC00654, LINC00710, LINC00226, LINC00326, LINC00494, LINC00535, LINC00616, LINC00662, LINC00668, LINC00467, LINC00608, and LINC00658) to show consistent differential expression across these studies. Some of the targets of these lncRNAs included CENPB, FAM98B, GOLGA6 family, RPGR, TPM2, GNB5, KCNQ10T1, TAZ, LIN28A, CDKN2B, CDKN2A, CDKN1A, CDKN1B, CDKN1C, EZH2, SUZ12, VEGFA genes. A lone study on human male infertility identified 9879 differentially expressed lncRNAs with three (lnc32058, lnc09522, and lnc98497) of them showing specific and high expression in immotile sperm in comparison to normal motile sperm. A few lncRNAs (Mrhl, Drm, Spga-lncRNAs, NLC1-C, HongrES2, Tsx, LncRNA-tcam1, Tug1, Tesra, AK015322, Gm2044, and LncRNA033862) have been functionally validated for their roles in spermatogenesis. Apart from rodents and humans, studies on sheep and bull have also identified lncRNAs potentially important for spermatogenesis. A number of these non-coding RNAs are strong candidates for further research on their roles in spermatogenesis.
State of the art technologies to explore long non‐coding RNAs in cancer
Long non‐coding RNAs (lncRNAs) comprise a vast repertoire of RNAs playing a wide variety of crucial roles in tissue physiology in a cell‐specific manner. Despite being engaged in myriads of regulatory mechanisms, many lncRNAs have still remained to be assigned any functions. A constellation of experimental techniques including single‐molecule RNA in situ hybridization (sm‐RNA FISH), cross‐linking and immunoprecipitation (CLIP), RNA interference (RNAi), Clustered regularly interspaced short palindromic repeats (CRISPR) and so forth has been employed to shed light on lncRNA cellular localization, structure, interaction networks and functions. Here, we review these and other experimental approaches in common use for identification and characterization of lncRNAs, particularly those involved in different types of cancer, with focus on merits and demerits of each technique.
A Primate‐Specific lncRNA LINC01021 Contributes to Cellular and Organismal Aging via DAZAP1‐Dependent Destabilization of RBMX
Aging is characterized by progressive physiological decline and age‐related pathologies, yet the molecular determinants underlying lineage‐ and species‐specific aging traits remain poorly understood. Although protein‐coding regulators have dominated aging research, the contribution of long non‐coding RNAs (lncRNAs), particularly primate‐specific lncRNAs, has not been systematically explored. Here, through evolutionary screening and cross‐species aging‐associated analyses, we identified a set of primate‐specific lncRNAs (including LINC01021, CTC‐575 l10.1, CTA‐150C2.13, and RP11‐305F18.1, etc.) associated with human aging, and we functionally characterized LINC01021 as a representative candidate to assess their causal involvement. In human cells, LINC01021 promotes cellular senescence, whereas its silencing attenuates senescence‐associated phenotypes. Mechanistically, LINC01021 is predominantly located in the nucleus, where it facilitates DAZAP1‐dependent destabilization of RBMX mRNA, leading to activation of the P53 pathway and induction of canonical senescence features. At the organismal level, ectopic expression of human LINC01021 in mice contributes to aging‐like phenotypes, including increased frailty and impaired motor coordination. Together, these findings implicate primate‐specific lncRNAs in lineage‐restricted aging and highlight an evolutionarily recent regulatory layer that may modulate aging trajectories. Primate‐specific lncRNA LINC01021 promotes aging by enhancing cellular senescence and accelerating aspects of organismal decline. Mechanistically, LINC01021 induces DAZAP1‐mediated destabilization of RBMX, activating the P53 pathway and establishing a primate‐specific regulatory axis in aging.
Spotlight on HOX cluster-embedded antisense lncRNAs in cardiovascular diseases (Review)
Atherosclerosis is a complex and chronic inflammatory disease driven by multiple pathophysiological processes that are responsible for diverse cardiovascular events. Atherosclerotic cardiovascular disease, despite substantial triumphs in primary and secondary prevention, remains a dominant epidemic that impairs human health. Therefore, deciphering the pathogenesis of atherosclerosis will provide a real-world translational understanding. Homeobox cluster-embedded antisense long non-coding RNAs (HOX-lncRNAs), a nascent class of lncRNA molecules with versatile roles in cancer, can also orchestrate various cell functions in cardiovascular disorders and have thus captured the attention of many researchers. Subsequently, numerous studies have demonstrated the role of HOX-lncRNAs as potential modulators of atherosclerosis. Nevertheless, given that the understanding of HOX-lncRNAs in atherosclerosis is only just emerging, ongoing research must be initiated to thoroughly pinpoint such causal roles. The present review aimed to highlight the important contributions of HOX-lncRNAs to atherosclerosis and other pivotal biological processes related to cardiovascular disease. The review concludes with a discussion of the limitations, outlook, challenges and possible solutions associated with HOX-lncRNAs in atherosclerosis. Looking forward, this may lead to extraordinary breakthroughs in revealing the molecular underpinnings of HOX-lncRNAs and may offer a promising yet challenging landscape for robust therapeutic strategies for atherosclerosis and/or associated cardiovascular disorders.
Smad3 Signatures in Renal Inflammation and Fibrosis
Renal inflammation and fibrosis are key pathological features of acute kidney injury (AKI) and chronic kidney disease (CKD). Smad3 is a critical mediator of TGF-β signaling and plays a pathogenic role in both renal inflammation and fibrosis. Smad3 can be activated not only by TGF-β1 but also by many stress molecules including angiotensin II (Ang II), advanced end products (AGEs), and C-reactive protein (CRP) under disease conditions. In addition, Smad3 can interact with other signaling pathways, such as the ERK/p38 MAPK and NF-κB pathways, to mediate renal inflammation and fibrosis. Mechanistically, Smad3 transcriptionally regulates many downstream target genes including microRNAs and long non-coding RNAs to cause cell death, inflammation, and fibrosis. Thus, targeting Smad3 or its downstream genes specifically related to renal inflammation and fibrosis should provide a novel therapeutic strategy to combat kidney diseases.
Unveiling the functions of five recently characterized lncRNAs in cancer progression
Numerous studies over the past few decades have shown that RNAs are multifaceted, multifunctional regulators of most cellular processes, contrary to the initial belief that they only act as mediators for translating DNA into proteins. LncRNAs, which refer to transcripts longer than 200nt and lack the ability to code for proteins, have recently been identified as central regulators of a variety of biochemical and cellular processes, particularly cancer. When they are abnormally expressed, they are closely associated with tumor occurrence, metastasis, and tumor staging. Therefore, through searches on Google Scholar, PubMed, and CNKI, we identified five five recently characterized lncRNAs–Lnc-SLC2A12-10:1, LncRNA BCRT1, lncRNA IGFBP4-1, LncRNA PCNAP1, and LncRNA CDC6–that have been linked to the promotion of cancer cell proliferation, invasion, and metastasis. Consequently, this review encapsulates the existing research and molecular underpinnings of these five newly identified lncRNAs across various types of cancer. It suggests that these novel lncRNAs hold potential as independent biomarkers for clinical diagnosis and prognosis, as well as candidates for therapeutic intervention. In parallel, we discuss the challenges inherent in the research on these five newly discovered lncRNAs and look forward to the avenues for future exploration in this field.
Plant long non-coding RNAs: identification and analysis to unveil their physiological functions
Eukaryotic genomes encode thousands of RNA molecules; however, only a minimal fraction is translated into proteins. Among the non-coding elements, long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. LncRNAs are associated mainly with the regulation of the expression of the genome; nonetheless, their study has just scratched the surface. This is somewhat due to the lack of widespread conservation at the sequence level, in addition to their relatively low and highly tissue-specific expression patterns, which makes their exploration challenging, especially in plant genomes where only a few of these molecules have been described completely. Recently published high-quality genomes of crop plants, along with new computational tools, are considered promising resources for studying these molecules in plants. This review briefly summarizes the characteristics of plant lncRNAs, their presence and conservation, the different protocols to find these elements, and the limitations of these protocols. Likewise, it describes their roles in different plant physiological phenomena. We believe that the study of lncRNAs can help to design strategies to reduce the negative effect of biotic and abiotic stresses on the yield of crop plants and, in the future, help create fruits and vegetables with improved nutritional content, higher amounts of compounds with positive effects on human health, better organoleptic characteristics, and fruits with a longer postharvest shelf life.