Long Noncoding RNAs and Their Therapeutic Promise in Diabetic Nephropathy

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Several important questions regarding the functionality of lncRNAs and their impact in kidney diseases, however, remain to be carefully addressed. Here, we provide an overview of the main functions and mechanisms of actions of lncRNAs, and their promise as therapeutic targets in kidney diseases, emphasizing on the role of some of the best-characterized lncRNAs implicated in the pathogenesis and progression of diabetic nephropathy.

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Long Noncoding RNAs: Recent Insights into Their Role in Male Infertility and Their Potential as Biomarkers and Therapeutic Targets

International Journal of Molecular Sciences ◽

10.3390/ijms222413579 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13579

Author(s):

Shanjiang Zhao ◽

Nuo Heng ◽

Bahlibi Weldegebriall Sahlu ◽

Huan Wang ◽

Huabin Zhu

Keyword(s):

Male Infertility ◽

Rna Polymerase Ii ◽

High Throughput Sequencing ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Long Noncoding Rnas ◽

Male Reproduction ◽

Biological Processes ◽

Stem Cell Pluripotency

Long noncoding RNAs (lncRNAs) are composed of nucleotides located in the nucleus and cytoplasm; these are transcribed by RNA polymerase II and are greater than 200 nt in length. LncRNAs fulfill important functions in a variety of biological processes, including genome imprinting, cell differentiation, apoptosis, stem cell pluripotency, X chromosome inactivation and nuclear transport. As high throughput sequencing technology develops, a substantial number of lncRNAs have been found to be related to a variety of biological processes, such as development of the testes, maintaining the self-renewal and differentiation of spermatogonial stem cells, and regulating spermatocyte meiosis. These indicate that lncRNAs can be used as biomarkers and potential therapeutic targets for male infertility. However, only a few comprehensive reviews have described the role of lncRNAs in male reproduction. In this paper, we summarize recent findings relating to the role of lncRNAs in spermatogenesis, their potential as biomarkers for male infertility and the relationship between reproductive arrest and transgenerational effects. Finally, we suggest specific targets for the treatment of male infertility from the perspective of lncRNAs.

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Interactions among Long Non-Coding RNAs and microRNAs Influence Disease Phenotype in Diabetes and Diabetic Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22116027 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6027

Author(s):

Swayam Prakash Srivastava ◽

Julie E. Goodwin ◽

Pratima Tripathi ◽

Keizo Kanasaki ◽

Daisuke Koya

Keyword(s):

Kidney Disease ◽

Large Scale ◽

Diabetic Kidney Disease ◽

Kidney Diseases ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Disease Phenotype ◽

Aberrant Expression ◽

Diabetic Kidney ◽

Health And Disease

Large-scale RNA sequencing and genome-wide profiling data revealed the identification of a heterogeneous group of noncoding RNAs, known as long noncoding RNAs (lncRNAs). These lncRNAs play central roles in health and disease processes in diabetes and cancer. The critical association between aberrant expression of lncRNAs in diabetes and diabetic kidney disease have been reported. LncRNAs regulate diverse targets and can function as sponges for regulatory microRNAs, which influence disease phenotype in the kidneys. Importantly, lncRNAs and microRNAs may regulate bidirectional or crosstalk mechanisms, which need to be further investigated. These studies offer the novel possibility that lncRNAs may be used as potential therapeutic targets for diabetes and diabetic kidney diseases. Here, we discuss the functions and mechanisms of actions of lncRNAs, and their crosstalk interactions with microRNAs, which provide insight and promise as therapeutic targets, emphasizing their role in the pathogenesis of diabetes and diabetic kidney disease

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Genome-Wide Identification and Characterization of Long Noncoding RNAs Involved in Chinese Wheat Mosaic Virus Infection of Nicotiana benthamiana

Biology ◽

10.3390/biology10030232 ◽

2021 ◽

Vol 10 (3) ◽

pp. 232

Author(s):

Weiran Zheng ◽

Haichao Hu ◽

Qisen Lu ◽

Peng Jin ◽

Linna Cai ◽

...

Keyword(s):

Virus Infection ◽

Mosaic Virus ◽

Nicotiana Benthamiana ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Genome Wide ◽

Chinese Wheat

Recent studies have shown that a large number of long noncoding RNAs (lncRNAs) can regulate various biological processes in animals and plants. Although lncRNAs have been identified in many plants, they have not been reported in the model plant Nicotiana benthamiana. Particularly, the role of lncRNAs in plant virus infection remains unknown. In this study, we identified lncRNAs in N. benthamiana response to Chinese wheat mosaic virus (CWMV) infection by RNA sequencing. A total of 1175 lncRNAs, including 65 differentially expressed lncRNAs, were identified during CWMV infection. We then analyzed the functions of some of these differentially expressed lncRNAs. Interestingly, one differentially expressed lncRNA, XLOC_006393, was found to participate in CWMV infection as a precursor to microRNAs in N. benthamiana. These results suggest that lncRNAs play an important role in the regulatory network of N. benthamiana in response to CWMV infection.

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Genome-wide discovery and characterization of long noncoding RNAs in patients with multiple myeloma

BMC Medical Genomics ◽

10.1186/s12920-019-0577-5 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Minqiu Lu ◽

Ying Hu ◽

Yin Wu ◽

Huixing Zhou ◽

Yuan Jian ◽

...

Keyword(s):

Multiple Myeloma ◽

Molecular Mechanisms ◽

Malignant Tumors ◽

Coiled Coil ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Aberrant Expression ◽

Genome Wide ◽

Wide Range ◽

Whole Transcriptome

Abstract Background Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes in tumorigenesis. However, the role of lncRNA expression in the biology, prognosis, and molecular classification of human multiple myeloma (MM) remains unclear, especially the biological functions of the vast majority of lncRNAs. Recently, lncRNAs have been identified in neoplastic hematologic disorders. Evidence has accumulated on the molecular mechanisms of action of lncRNAs, providing insight into their functional roles in tumorigenesis. This study aimed to characterize potential lncRNAs in patients with MM. Methods In this study, the whole-transcriptome strand-specific RNA sequencing of samples from three newly diagnosed patients with MM was performed. The whole transcriptome, including lncRNAs, microRNAs, and mRNAs, was analyzed. Using these data, MM lncRNAs were systematically analyzed, and the lncRNAs involved in the occurrence of MM were identified. Results The results revealed that MM lncRNAs had distinctive characteristics different from those of other malignant tumors. Further, the functions of a set of lncRNAs preferentially expressed in MM were verified, and several lncRNAs were identified as competing endogenous RNAs. More importantly, the aberrant expression of certain lncRNAs, including maternally expressed gene3, colon cancer–associated transcript1, and coiled-coil domain-containing 26, as well as some novel lncRNAs involved in the occurrence of MM was established. Further, lncRNAs were related to some microRNAs, regulated each other, and participated in MM development. Conclusions Genome-wide screening and functional analysis enabled the identification of a set of lncRNAs involved in the occurrence of MM. The interaction exists among microRNAs and lncRNAs.

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The role of the retinoids in schizophrenia: genomic and clinical perspectives

Molecular Psychiatry ◽

10.1038/s41380-019-0566-2 ◽

2019 ◽

Vol 25 (4) ◽

pp. 706-718 ◽

Cited By ~ 8

Author(s):

William R. Reay ◽

Murray J. Cairns

Keyword(s):

Vitamin A ◽

Embryonic Development ◽

Human Brain ◽

Observational Data ◽

Large Scale ◽

Dietary Intervention ◽

Biological Processes ◽

Master Regulators ◽

Genome Wide

Abstract Signalling by retinoid compounds is vital for embryonic development, with particular importance for neurogenesis in the human brain. Retinoids, metabolites of vitamin A, exert influence over the expression of thousands of transcripts genome wide, and thus, act as master regulators of many important biological processes. A significant body of evidence in the literature now supports dysregulation of the retinoid system as being involved in the aetiology of schizophrenia. This includes mechanistic insights from large-scale genomic, transcriptomic and, proteomic studies, which implicate disruption of disparate aspects of retinoid biology such as transport, metabolism, and signalling. As a result, retinoids may present a valuable clinical opportunity in schizophrenia via novel pharmacotherapies and dietary intervention. Further work, however, is required to expand on the largely observational data collected thus far and confirm causality. This review will highlight the fundamentals of retinoid biology and examine the evidence for retinoid dysregulation in schizophrenia.

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Role of Long Noncoding RNAs in Parkinson’s Disease: Putative Biomarkers and Therapeutic Targets

Parkinson s Disease ◽

10.1155/2020/5374307 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Qiankun Lv ◽

Ziyu Wang ◽

Zhen Zhong ◽

Wei Huang

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Alpha Synuclein ◽

Long Noncoding Rnas ◽

Main Risk Factor ◽

Diagnostic Biomarkers ◽

Rna Molecules

Parkinson’s disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, and tremor. Age is the main risk factor. Long noncoding RNAs (lncRNAs) are novel RNA molecules of more than 200 nucleotides in length. They may be involved in the regulation of many pathological processes of PD. PD has a variety of pathophysiological mechanisms, including alpha-synuclein aggregate, mitochondrial dysfunction, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation. Among these, the impacts of lncRNAs on the pathogenesis and progression of PD need to be highlighted. lncRNAs may serve as putative biomarkers and therapeutic targets for the early diagnosis of PD. This study aimed to investigate the role of lncRNAs in various pathological processes of PD and the specific lncRNAs that might be used as putative diagnostic biomarkers and therapeutic targets of PD.

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Coding of Glioblastoma Progression and Therapy Resistance through Long Noncoding RNAs

Cancers ◽

10.3390/cancers12071842 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1842 ◽

Cited By ~ 2

Author(s):

Alja Zottel ◽

Neja Šamec ◽

Alja Videtič Paska ◽

Ivana Jovčevska

Keyword(s):

Large Scale ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Therapy Resistance ◽

Long Noncoding Rnas ◽

Major Step ◽

Genomic Complexity ◽

Average Patient ◽

Definition Of

Glioblastoma is the most aggressive and lethal primary brain malignancy, with an average patient survival from diagnosis of 14 months. Glioblastoma also usually progresses as a more invasive phenotype after initial treatment. A major step forward in our understanding of the nature of glioblastoma was achieved with large-scale expression analysis. However, due to genomic complexity and heterogeneity, transcriptomics alone is not enough to define the glioblastoma “fingerprint”, so epigenetic mechanisms are being examined, including the noncoding genome. On the basis of their tissue specificity, long noncoding RNAs (lncRNAs) are being explored as new diagnostic and therapeutic targets. In addition, growing evidence indicates that lncRNAs have various roles in resistance to glioblastoma therapies (e.g., MALAT1, H19) and in glioblastoma progression (e.g., CRNDE, HOTAIRM1, ASLNC22381, ASLNC20819). Investigations have also focused on the prognostic value of lncRNAs, as well as the definition of the molecular signatures of glioma, to provide more precise tumor classification. This review discusses the potential that lncRNAs hold for the development of novel diagnostic and, hopefully, therapeutic targets that can contribute to prolonged survival and improved quality of life for patients with glioblastoma.

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Comprehensive pathway analyses of schizophrenia risk loci point to dysfunctional postsynaptic signaling

10.1101/117481 ◽

2017 ◽

Cited By ~ 2

Author(s):

Dick Schijven ◽

Daniel Kofink ◽

Vinicius Tragante ◽

Marloes Verkerke ◽

Sara L. Pulit ◽

...

Keyword(s):

Large Scale ◽

Expression Profiles ◽

Association Studies ◽

Enrichment Analysis ◽

Large Contribution ◽

Genome Wide Association Studies ◽

Biological Processes ◽

Gene Set ◽

Genome Wide

AbstractLarge-scale genome-wide association studies (GWAS) have implicated many low-penetrance loci in schizophrenia. However, its pathological mechanisms are poorly understood, which in turn hampers the development of novel pharmacological treatments. Pathway and gene set analyses carry the potential to generate hypotheses about disease mechanisms and have provided biological context to genome-wide data of schizophrenia. We aimed to examine which biological processes are likely candidates to underlie schizophrenia by integrating novel and powerful pathway analysis tools using data from the largest Psychiatric Genomics Consortium schizophrenia GWAS (N = 79 845) and the most recent 2018 schizophrenia GWAS (N = 105 318). By applying a primary unbiased analysis (Multi-marker Analysis of GenoMic Annotation; MAGMA) to weigh the role of biological processes from the MSigDB database, we identified enrichment of common variants in synaptic plasticity and neuron differentiation gene sets. We supported these findings using MAGMA, Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA) and Interval Enrichment Analysis (INRICH) on detailed synaptic signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and found enrichment in mainly the dopaminergic and cholinergic synapses. Moreover, shared genes involved in these neurotransmitter systems had a large contribution to the observed enrichment, protein products of top genes in these pathways showed more direct and indirect interactions than expected by chance, and expression profiles of these genes were largely similar among brain tissues. In conclusion, we provide strong and consistent genetics and protein-interaction informed evidence for the role of postsynaptic signaling processes in schizophrenia, opening avenues for future translational and psychopharmacological studies.

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Emerging Role of Exosomal-Derived Long Noncoding RNAs in Human PDAC

Visceral Medicine ◽

10.1159/000520947 ◽

2021 ◽

pp. 1-7

Author(s):

Di Long ◽

Xiao Dong Tian ◽

Yin-Mo Yang

Keyword(s):

Early Diagnosis ◽

Prognostic Markers ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Long Noncoding Rnas ◽

Current Status ◽

Ductal Adenocarcinoma ◽

Advanced Stage ◽

Incidence And Mortality

Background: The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are increasing recently. Most patients with PDAC are diagnosed at advanced stage because of the high invasiveness of cancer cells and the lack of typical early symptoms. Therefore, early diagnosis of PDAC is very important to improve the prognosis. Exosomes play crucial role in intercellular communication and deliver the contents to recipient cells to regulate their biological behaviors. Recent evidence suggests emerging role of exosomes in the carcinogenesis of a variety of cancers including PDAC. Long noncoding RNAs (LncRNAs) have been reported to be involved in the development of PDAC. It has been proved that LncRNAs have the potential to be biomarkers and therapeutic targets for PDAC. Moreover, increasing number of studies focus on the role of exosomal LncRNAs in PDAC. Summary: In this review, we summarize the current status on our understanding of the role of exosomal-derived LncRNAs in the progression and metastasis of PDAC. Key Messages: We focus on challenges in the potential of exosomal-derived LncRNAs as novel diagnostic and prognostic markers and therapeutic targets of PDAC. In addition, we provide an overview about the demonstrated important role of exosomal LncRNAs in the progression of PDAC.

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lncRedibly versatile: biochemical and biological functions of long noncoding RNAs

Biochemical Journal ◽

10.1042/bcj20180440 ◽

2019 ◽

Vol 476 (7) ◽

pp. 1083-1104 ◽

Cited By ~ 8

Author(s):

Emily J. Shields ◽

Ana F. Petracovici ◽

Roberto Bonasio

Keyword(s):

Protein Interactions ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Biological Processes ◽

Biological Functions ◽

Protein Protein Interactions ◽

Biological Mechanisms ◽

Genome Wide ◽

Regulatory Effects ◽

Exciting Time

Abstract Long noncoding RNAs (lncRNAs) are transcripts that do not code for proteins, but nevertheless exert regulatory effects on various biochemical pathways, in part via interactions with proteins, DNA, and other RNAs. LncRNAs are thought to regulate transcription and other biological processes by acting, for example, as guides that target proteins to chromatin, scaffolds that facilitate protein–protein interactions and complex formation, and orchestrators of phase-separated compartments. The study of lncRNAs has reached an exciting time, as recent advances in experimental and computational methods allow for genome-wide interrogation of biochemical and biological mechanisms of these enigmatic transcripts. A better appreciation for the biochemical versatility of lncRNAs has allowed us to begin closing gaps in our knowledge of how they act in diverse cellular and organismal contexts, including development and disease.

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