Harnessing the potential of long non-coding RNAs to manage metabolic diseases

2021 ◽  
Vol 27 ◽  
Author(s):  
Khushdeep Bandesh ◽  
Daisy Masih ◽  
Nirjhar Bhattacharyya ◽  
Dwaipayan Bharadwaj

: Long non-coding RNAs (lncRNAs) are functionally versatile molecules that regulate gene expression at all levels of biological organization. RNA modulation, at the moment, has emerged as a powerful therapeutic technique to treat human diseases. Lately, lncRNAs have been acknowledged as key players in human metabolism and, indeed, implicated in the etiology of many common diseases other than cancers, where they can perhaps serve as reliable markers to determine disease status or assess outcomes of an intervention. Here, in this review, we cite examples of such lncRNAs, discuss their mechanistic role in human diseases and their genetic association, quote potential biomarkers found in human blood, summarize the methods for therapeutic targeting lncRNAs and examine the progress of lncRNA based drugs in clinical trials. Thus, we propose that lncRNAs serve as both a biomarker and an effective therapeutic target with promising clinical utility to manage human metabolic diseases.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Sadoughi ◽  
Seyyed Mehdi Mirhashemi ◽  
Zatollah Asemi

AbstractSmall non‐coding RNAs (sncRNAs) are a subgroup of non‐coding RNAs, with less than 200 nucleotides length and no potential for coding proteins. PiRNAs, a member of sncRNAs, were first discovered more than a decade ago and have attracted researcher’s attention because of their gene regulatory function both in the nucleus and in the cytoplasm. Recent investigations have found that the abnormal expression of these sncRNAs is involved in many human diseases, including cancers. Colorectal cancer (CRC), as a common gastrointestinal malignancy, is one of the important causes of cancer‐related deaths through the entire world and appears to be a consequence of mutation in the genome and epigenetic alterations. The aim of this review is to realize whether there is a relationship between CRC and piRNAs or not.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ellie J. Putz ◽  
Austin M. Putz ◽  
Hyeongseon Jeon ◽  
John D. Lippolis ◽  
Hao Ma ◽  
...  

AbstractIn dairy cows, the period from the end of lactation through the dry period and into the transition period, requires vast physiological and immunological changes critical to mammary health. The dry period is important to the success of the next lactation and intramammary infections during the dry period will adversely alter mammary function, health and milk production for the subsequent lactation. MicroRNAs (miRNAs) are small non-coding RNAs that can post transcriptionally regulate gene expression. We sought to characterize the miRNA profile in dry secretions from the last day of lactation to 3, 10, and 21 days post dry-off. We identified 816 known and 80 novel miRNAs. We found 46 miRNAs whose expression significantly changed (q-value < 0.05) over the first three weeks of dry-off. Additionally, we examined the slopes of random regression models of log transformed normalized counts and cross analyzed the 46 significantly upregulated and downregulated miRNAs. These miRNAs were found to be associated with important components of pregnancy, lactation, as well as inflammation and disease. Detailing the miRNA profile of dry secretions through the dry-off period provides insight into the biology at work, possible means of regulation, components of resistance and/or susceptibility, and outlets for targeted therapy development.


2021 ◽  
Vol 22 (6) ◽  
pp. 2904
Author(s):  
Peiyu Zhu ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
Guangcai Duan ◽  
Yuefei Jin

Enteroviruses (EVs) are common RNA viruses that can cause various types of human diseases and conditions such as hand, foot, and mouth disease (HFMD), myocarditis, meningitis, sepsis, and respiratory disorders. Although EV infections in most patients are generally mild and self-limiting, a small number of young children can develop serious complications such as encephalitis, acute flaccid paralysis, myocarditis, and cardiorespiratory failure, resulting in fatalities. Established evidence has suggested that certain non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) are involved in the occurrence and progression of many human diseases. Recently, the involvement of ncRNAs in the course of EV infection has been reported. Herein, the authors focus on recent advances in the understanding of ncRNAs in EV infection from basic viral pathogenesis to clinical prospects, providing a reference basis and new ideas for disease prevention and research directions.


Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 167 ◽  
Author(s):  
Muhammad Nawaz ◽  
Neelam Shah ◽  
Bruna Zanetti ◽  
Marco Maugeri ◽  
Renata Silvestre ◽  
...  

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shihu Jiao ◽  
Song Wu ◽  
Shan Huang ◽  
Mingyang Liu ◽  
Bo Gao

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a closed-loop structure that are mainly produced by variable processing of precursor mRNAs (pre-mRNAs). They are widely present in all eukaryotes and are very stable. Currently, circRNA studies have become a hotspot in RNA research. It has been reported that circRNAs constitute a significant proportion of transcript expression, and some are significantly more abundantly expressed than other transcripts. CircRNAs have regulatory roles in gene expression and critical biological functions in the development of organisms, such as acting as microRNA sponges or as endogenous RNAs and biomarkers. As such, they may have useful functions in the diagnosis and treatment of diseases. CircRNAs have been found to play an important role in the development of several diseases, including atherosclerosis, neurological disorders, diabetes, and cancer. In this paper, we review the status of circRNA research, describe circRNA-related databases and the identification of circRNAs, discuss the role of circRNAs in human diseases such as colon cancer, atherosclerosis, and gastric cancer, and identify remaining research questions related to circRNAs.


2008 ◽  
Vol 114 (12) ◽  
pp. 699-706 ◽  
Author(s):  
Chunxiang Zhang

miRNAs (microRNAs) comprise a novel class of endogenous, small, non-coding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Recent studies have demonstrated that miRNAs are highly expressed in the cardiovascular system. Although we are currently in the initial stages of understanding how this novel class of gene regulators is involved in cardiovascular biological functions, a growing body of exciting evidence suggests that miRNAs are important regulators of cardiovascular cell differentiation, growth, proliferation and apoptosis. Moreover, miRNAs are key modulators of both cardiovascular development and angiogenesis. Consequently, dysregulation of miRNA function may lead to cardiovascular diseases. Indeed, several recent reports have demonstrated that miRNAs are aberrantly expressed in diseased hearts and vessels. Modulating these aberrantly expressed miRNAs has significant effects on cardiac hypertrophy, vascular neointimal lesion formation and cardiac arrhythmias. Identifying the roles of miRNAs and their target genes and signalling pathways in cardiovascular disease will be critical for future research. miRNAs may represent a new layer of regulators for cardiovascular biology and a novel class of therapeutic targets for cardiovascular diseases.


2019 ◽  
Vol 401 (1) ◽  
pp. 3-29 ◽  
Author(s):  
Bradford G. Hill ◽  
Sruti Shiva ◽  
Scott Ballinger ◽  
Jianhua Zhang ◽  
Victor M. Darley-Usmar

AbstractIt is now becoming clear that human metabolism is extremely plastic and varies substantially between healthy individuals. Understanding the biochemistry that underlies this physiology will enable personalized clinical interventions related to metabolism. Mitochondrial quality control and the detailed mechanisms of mitochondrial energy generation are central to understanding susceptibility to pathologies associated with aging including cancer, cardiac and neurodegenerative diseases. A precision medicine approach is also needed to evaluate the impact of exercise or caloric restriction on health. In this review, we discuss how technical advances in assessing mitochondrial genetics, cellular bioenergetics and metabolomics offer new insights into developing metabolism-based clinical tests and metabolotherapies. We discuss informatics approaches, which can define the bioenergetic-metabolite interactome and how this can help define healthy energetics. We propose that a personalized medicine approach that integrates metabolism and bioenergetics with physiologic parameters is central for understanding the pathophysiology of diseases with a metabolic etiology. New approaches that measure energetics and metabolomics from cells isolated from human blood or tissues can be of diagnostic and prognostic value to precision medicine. This is particularly significant with the development of new metabolotherapies, such as mitochondrial transplantation, which could help treat complex metabolic diseases.


Author(s):  
Hongying Zhao ◽  
Jian Shi ◽  
Yunpeng Zhang ◽  
Aimin Xie ◽  
Lei Yu ◽  
...  

Abstract Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA–disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA–target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA–target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA–target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA–target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.


2020 ◽  
Vol 14 (01) ◽  
pp. 15-29
Author(s):  
Somsubhro Mukherjee ◽  
Boon Chuan Low

Scaffold proteins are critical regulators of important cell signaling pathways. Though scaffolds are not stringently defined in meaning, they are known to interact with numerous components of a signaling pathway, binding and bridging them into distinct and functional complexes. They control signal transduction and assist the localization of pathway components (organized in complexes) to definite regions of the cell such as the endosomes, plasma membrane, the cytoplasm, mitochondria, Golgi, and the nucleus. Years of research in this field have revealed the versatility of this class of protein and the important role it plays in maintaining the normal functions of the human body. Here, we discuss the role of several scaffold proteins which are implicated in important signaling pathways that play important roles in cardiac diseases, metabolic diseases, neurological disorders, and cancer. Their versatility and functions in human diseases make them attractive drug targets, several of which have been investigated in clinical trials. Future studies of scaffold proteins should give us an in-depth knowledge of how cell signaling works in normal and pathological conditions and would offer avenues to disrupt harmful cellular pathways to circumvent diseases.


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