Oligonucleotide Analogues as Modulators of the Expression and Function of Noncoding RNAs (ncRNAs): Emerging Therapeutics Applications

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

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Identification and function annotation of long intervening noncoding RNAs

Briefings in Bioinformatics ◽

10.1093/bib/bbw046 ◽

2016 ◽

pp. bbw046 ◽

Cited By ~ 8

Author(s):

Haitao Luo ◽

Dechao Bu ◽

Liang Sun ◽

Shuangsang Fang ◽

Zhiyong Liu ◽

...

Keyword(s):

Noncoding Rnas ◽

Function Annotation ◽

And Function

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Construction of an lncRNA–mRNA Co-Expression Regulatory Network Mediating Inflammation and Regeneration Following Acute Pancreatitis Injury

10.21203/rs.3.rs-1152574/v1 ◽

2021 ◽

Author(s):

Jing Wang ◽

Tianjie Chen ◽

Xiaohua Zhang ◽

Shulei Zhao

Keyword(s):

Acute Pancreatitis ◽

Mrna Expression ◽

Regulatory Network ◽

Noncoding Rnas ◽

Pancreatic Injury ◽

Control Group ◽

Rna Seq ◽

Damage Repair ◽

Injury And Repair ◽

And Function

Abstract Long noncoding RNAs (lncRNAs) play important roles in the occurrence and development of many diseases and can be used as targets for diagnosis and treatment. However, the expression and function of lncRNAs in the injury and repair of acute pancreatitis (AP) are unclear. To decipher lncRNAs’ regulatory roles in AP, we reanalyzed an RNA-seq dataset of 24 pancreatic tissues, including those of normal control mice (BL), those 7 days after mild AP (D7), and those 14 days after mild AP (D14). The results showed significant differences in lncRNA and mRNA expression of D7/D14 groups compared with the control group. Co-expression analysis showed that differentially expressed (DE) lncRNAs were closely related to immunity- and inflammation-related pathways by trans-regulating mRNA expression. The lncRNA–mRNA network showed that the lncRNAs Dancer, Gmm20488, Terc, Snhg3, and Snhg20 were significantly correlated with AP pathogenesis. WGCNA and cis regulation analysis also showed that AP repair-associated lncRNAs were correlated with extracellular and inflammation-related genes, which affect the repair and regeneration of pancreatic injury after AP. In conclusion, the systemic dysregulation of lncRNAs is strongly involved in remodeling AP’s gene expression regulatory network, and the lncRNA–mRNA expression network could identify targets for AP treatment and damage repair.

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The Roles of Long Noncoding RNAs HNF1α-AS1 and HNF4α-AS1 in Drug Metabolism and Human Diseases

Non-Coding RNA ◽

10.3390/ncrna6020024 ◽

2020 ◽

Vol 6 (2) ◽

pp. 24 ◽

Cited By ~ 1

Author(s):

Liming Chen ◽

Yifan Bao ◽

Suzhen Jiang ◽

Xiao-bo Zhong

Keyword(s):

Drug Metabolism ◽

Drug Toxicity ◽

Target Genes ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Future Directions ◽

Protein Coding ◽

Mirna Sponge ◽

Current Review ◽

And Function

Long noncoding RNAs (lncRNAs) are RNAs with a length of over 200 nucleotides that do not have protein-coding abilities. Recent studies suggest that lncRNAs are highly involved in physiological functions and diseases. lncRNAs HNF1α-AS1 and HNF4α-AS1 are transcripts of lncRNA genes HNF1α-AS1 and HNF4α-AS1, which are antisense lncRNA genes located in the neighborhood regions of the transcription factor (TF) genes HNF1α and HNF4α, respectively. HNF1α-AS1 and HNF4α-AS1 have been reported to be involved in several important functions in human physiological activities and diseases. In the liver, HNF1α-AS1 and HNF4α-AS1 regulate the expression and function of several drug-metabolizing cytochrome P450 (P450) enzymes, which also further impact P450-mediated drug metabolism and drug toxicity. In addition, HNF1α-AS1 and HNF4α-AS1 also play important roles in the tumorigenesis, progression, invasion, and treatment outcome of several cancers. Through interacting with different molecules, including miRNAs and proteins, HNF1α-AS1 and HNF4α-AS1 can regulate their target genes in several different mechanisms including miRNA sponge, decoy, or scaffold. The purpose of the current review is to summarize the identified functions and mechanisms of HNF1α-AS1 and HNF4α-AS1 and to discuss the future directions of research of these two lncRNAs.

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Current Research Progress on Long Noncoding RNAs Associated with Hepatocellular Carcinoma

Analytical Cellular Pathology ◽

10.1155/2019/1534607 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Haihong Shi ◽

Yuxin Xu ◽

Xin Yi ◽

Dandan Fang ◽

Xia Hou

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Liver Cancer ◽

Biological Activities ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Research Progress ◽

Invasion And Metastasis ◽

Complex Processes ◽

And Function

Hepatocellular carcinoma (HCC) is the second leading cause of mortality among cancers. It has been found that long noncoding RNAs (lncRNAs) are involved in many human cancers, including liver cancer. It has been identified that carcinogenic and tumor-suppressing lncRNAs are associated with complex processes in liver cancer. These lncRNAs may participate in a variety of pathological and biological activities, such as cell proliferation, apoptosis, invasion, and metastasis. Here, we review the regulation and function of lncRNA in liver cancer and evaluate the potential of lncRNA as a new goal for liver cancer.

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Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs

BioMed Research International ◽

10.1155/2017/7354260 ◽

2017 ◽

Vol 2017 ◽

pp. 1-38 ◽

Cited By ~ 13

Author(s):

María Antonia Lizarbe ◽

Jorge Calle-Espinosa ◽

Eva Fernández-Lizarbe ◽

Sara Fernández-Lizarbe ◽

Miguel Ángel Robles ◽

...

Keyword(s):

Colorectal Cancer ◽

Posttranscriptional Regulation ◽

Genetic Model ◽

Treatment Options ◽

Noncoding Rnas ◽

Developed Countries ◽

Colorectal Carcinogenesis ◽

Special Focus ◽

Epigenetic Alterations ◽

And Function

Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression. We present a general overview of what is known about these molecules and their role and dysregulation in cancer, with a special focus on the biogenesis, characteristics, and function of microRNAs. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in cancer, including colorectal cancer. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and efficacy of chemotherapeutic treatments, or even as therapeutic agents, or as targets by themselves. Thus, this review highlights the importance of miRNAs in the development, progression, diagnosis, and therapy of colorectal cancer and summarizes current therapeutic approaches for the treatment of colorectal cancer.

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MicroRNAs in Platelets: Should I Stay or Should I Go?

Platelets ◽

10.5772/intechopen.93181 ◽

2020 ◽

Author(s):

Sonia Águila ◽

Ernesto Cuenca-Zamora ◽

Constantino Martínez ◽

Raúl Teruel-Montoya

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Extracellular Vesicles ◽

Intercellular Communication ◽

Noncoding Rnas ◽

Signal Transduction Pathway ◽

Response To Therapy ◽

Transduction Pathway ◽

Small Noncoding Rnas ◽

And Function

In this chapter, we discuss different topics always using the microRNA as the guiding thread of the review. MicroRNAs, member of small noncoding RNAs family, are an important element involved in gene expression. We cover different issues such as their importance in the differentiation and maturation of megakaryocytes (megakaryopoiesis), as well as the role in platelets formation (thrombopoiesis) focusing on the described relationship between miRNA and critical myeloid lineage transcription factors such as RUNX1, chemokines receptors as CRCX4, or central hormones in platelet homeostasis like TPO, as well as its receptor (MPL) and the TPO signal transduction pathway, that is JAK/STAT. In addition to platelet biogenesis, we review the microRNA participation in platelets physiology and function. This review also introduces the use of miRNAs as biomarkers of platelet function since the detection of pathogenic situations or response to therapy using these noncoding RNAs is getting increasing interest in disease management. Finally, this chapter describes the participation of platelets in cellular interplay, since extracellular vesicles have been demonstrated to have the ability to deliver microRNAs to others cells, modulating their function through intercellular communication, redefining the extracellular vesicles from the so-called “platelet dust” to become mediators of intercellular communication.

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Long non-coding RNAs in wild wheat progenitors

10.1101/301804 ◽

2018 ◽

Author(s):

Alice Pieri ◽

Mario Enrico Pè ◽

Edoardo Bertolini

Keyword(s):

Aegilops Tauschii ◽

Noncoding Rnas ◽

Reproductive Organs ◽

Long Noncoding Rnas ◽

D Genome ◽

Specific Expression ◽

Wild Wheat ◽

Organ Specific ◽

Species Specific ◽

And Function

AbstractTriticum urartu and Aegilops tauschii are the diploid progenitors of the hexaploid Triticum aestivum (AuAuBBDD), donors of the Au and D genome respectively. In this work we investigate the long noncoding RNAs (lncRNAs) component of the genomes of these two wild wheat relatives. Sixty-eight RNA-seq libraries generated from several organs and conditions were retrieved from public databases. We annotated and characterized 14,515 T. urartu and 20,908 Ae. tauschii bona-fide lncRNA transcripts that show features similar to those of other plant and animal counterparts. Thousands of lncRNAs were found significantly modulated in different organs and exhibited organ specific expression, with a predominant accumulation in the spike, fostering the hypothesis of their crucial role in reproductive organs. Most of the organ-specific lncRNAs were found associated with transposable elements (TEs), indicating the possible role of TEs in lncRNA origin, differentiation and function. The majority of T. urartu and Ae. tauschii lncRNAs appear to be species-specific; nevertheless, we found some lncRNAs conserved between the two wheat progenitors, highlighting the presence and conservation of exonic splicing enhancers sites in multi-exon conserved lncRNAs. In addition, we found cases of lncRNA conservation and their cis regulatory regions spanning the wheat pre-domestication and post-domestication period. Altogether, these results represent the first comprehensive genome-wide encyclopedia of lncRNAs in wild wheat relatives, and they provide clues as to the hidden regulatory pathway mediated by long noncoding RNAs in these largely unexplored wheat progenitors.

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Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications

Biomedicines ◽

10.3390/biomedicines9111509 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1509

Author(s):

Rosaria Varì ◽

Beatrice Scazzocchio ◽

Tiziana Filardi ◽

Anna Citarella ◽

Maria Bellenghi ◽

...

Keyword(s):

Developmental Stages ◽

Noncoding Rnas ◽

Circular Rnas ◽

Sexually Dimorphic ◽

Fetal Sex ◽

Complex Interactions ◽

Physiological Processes ◽

Different Types ◽

And Function ◽

In Pregnancy

In the era of personalized medicine, fetal sex-specific research is of utmost importance for comprehending the mechanisms governing pregnancy and pregnancy-related complications. In recent times, noncoding RNAs (ncRNAs) have gained increasing attention as critical players in gene regulation and disease pathogenesis, and as candidate biomarkers in human diseases as well. Different types of ncRNAs, including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in every step of pregnancy progression, although studies taking into consideration fetal sex as a central variable are still limited. To date, most of the available data have been obtained investigating sex-specific placental miRNA expression. Several studies revealed that miRNAs regulate the (patho)-physiological processes in a sexually dimorphic manner, ensuring normal fetal development, successful pregnancy, and susceptibility to diseases. Moreover, the observation that ncRNA profiles differ according to cells, tissues, and developmental stages of pregnancy, along with the complex interactions among different types of ncRNAs in regulating gene expression, strongly indicates that more studies are needed to understand the role of sex-specific ncRNA in pregnancy and associated disorders.

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Ebola Virus Produces Discrete Small Noncoding RNAs Independently of the Host MicroRNA Pathway Which Lack RNA Interference Activity in Bat and Human Cells

Journal of Virology ◽

10.1128/jvi.01441-19 ◽

2019 ◽

Vol 94 (6) ◽

Cited By ~ 3

Author(s):

Abhishek N. Prasad ◽

Adam J. Ronk ◽

Steven G. Widen ◽

Thomas G. Wood ◽

Christopher F. Basler ◽

...

Keyword(s):

Ebola Virus ◽

Noncoding Rnas ◽

Computational Prediction ◽

Marburg Virus ◽

Sequencing Data ◽

Viral Mirnas ◽

Small Noncoding Rnas ◽

Bona Fide ◽

Mirna Pathway ◽

And Function

ABSTRACT The question as to whether RNA viruses produce bona fide microRNAs (miRNAs) during infection has been the focus of intense research and debate. Recently, several groups using computational prediction methods have independently reported possible miRNA candidates produced by Ebola virus (EBOV). Additionally, efforts to detect these predicted RNA products in samples from infected animals and humans have produced positive results. However, these studies and their conclusions are predicated on the assumption that these RNA products are actually processed through, and function within, the miRNA pathway. In the present study, we performed the first rigorous assessment of the ability of filoviruses to produce miRNA products during infection of both human and bat cells. Using next-generation sequencing, we detected several candidate miRNAs from both EBOV and the closely related Marburg virus (MARV). Focusing our validation efforts on EBOV, we found evidence contrary to the idea that these small RNA products function as miRNAs. The results of our study are important because they highlight the potential pitfalls of relying on computational methods alone for virus miRNA discovery. IMPORTANCE Here, we report the discovery, via deep sequencing, of numerous noncoding RNAs (ncRNAs) derived from both EBOV and MARV during infection of both bat and human cell lines. In addition to identifying several novel ncRNAs from both viruses, we identified two EBOV ncRNAs in our sequencing data that were near-matches to computationally predicted viral miRNAs reported in the literature. Using molecular and immunological techniques, we assessed the potential of EBOV ncRNAs to function as viral miRNAs. Importantly, we found little evidence supporting this hypothesis. Our work is significant because it represents the first rigorous assessment of the potential for EBOV to encode viral miRNAs and provides evidence contrary to the existing paradigm regarding the biological role of computationally predicted EBOV ncRNAs. Moreover, our work highlights further avenues of research regarding the nature and function of EBOV ncRNAs.

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