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17 pages, 6608 KiB

Open AccessArticle

Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs

by Salam Salloum-Asfar, Sara A. Abdulla, Rowaida Z. Taha, I. Richard Thompson and Mohamed M. Emara

Cells 2022, 11(23), 3833; https://doi.org/10.3390/cells11233833 - 29 Nov 2022

Viewed by 1385

Somatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage of transfected [...] Read more.

Somatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage of transfected cells can undergo full reprogramming. Introducing miRNAs, such as miR-294 and miR302/3667, with reprogramming factors, has shown to increase iPSC colony formation. Previously, we identified five transcription factors, GBX2, NANOGP8, SP8, PEG3, and ZIC1, which may boost iPSC generation. In this study, we performed quantitative miRNAome and small RNA-seq sequencing and applied our previously identified transcriptome to identify the potential miRNA–mRNA regulomics and regulatory network of other ncRNAs. From each fibroblast (N = 4), three iPSC clones were examined (N = 12). iPSCs and original fibroblasts expressed miRNA clusters differently and miRNA clusters were compared to mRNA hits. Moreover, miRNA, piRNA, and snoRNAs expression profiles in iPSCs and original fibroblasts were assessed to identify the potential role of ncRNAs in enhancing iPSC generation, pluripotency, and differentiation. Decreased levels of let-7a-5p showed an increase of SP8 as described previously. Remarkably, the targets of identifier miRNAs were grouped into pluripotency canonical pathways, on stemness, cellular development, growth and proliferation, cellular assembly, and organization of iPSCs. Full article

(This article belongs to the Special Issue The Mission of Non-coding RNAs in the Growth and Development of Stem Cells and in Treating Diseases)

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12 pages, 2114 KiB

Open AccessArticle

Lycopene Scavenges Cellular ROS, Modulates Autophagy and Improves Survival through 7SK snRNA Interaction in Smooth Muscle Cells

by Ayed A. Shati, Refaat A. Eid, Mohamed Samir A. Zaki, Youssef A. Alqahtani, Saleh M. Al-Qahtani and Harish C. Chandramoorthy

Cells 2022, 11(22), 3617; https://doi.org/10.3390/cells11223617 - 15 Nov 2022

Cited by 5 | Viewed by 1642

Abstract

The chance of survival rate and autophagy of smooth muscle cells under calcium stress were drastically improved with a prolonged inclusion of Lycopene in the media. The results showed an improved viability from 41% to 69% and a reduction in overall autophagic bodies [...] Read more.

The chance of survival rate and autophagy of smooth muscle cells under calcium stress were drastically improved with a prolonged inclusion of Lycopene in the media. The results showed an improved viability from 41% to 69% and a reduction in overall autophagic bodies from 7% to 3%, which was well in agreement with the LC3II and III mRNA levels. However, the proliferation was slow compared to the controls. The fall in the major inflammatory marker TNF-α and improved antioxidant enzyme GPx were regarded as significant restoration markers of cell survival. The reactive oxygen species (ROS) were reduced from 8 fold to 3 fold post addition of lycopene for 24 h. Further, the docking studies revealed binding of lycopene molecules with 7SK snRNA at 7.6 kcal/mol docking energy with 300 ns stability under physiological conditions. Together, these results suggest that Lycopene administration during ischemic heart disease might improve the functions of the smooth muscle cells and 7SK snRNA might be involved in the binding of lycopene and its antioxidant protective effects. Full article

(This article belongs to the Special Issue The Mission of Non-coding RNAs in the Growth and Development of Stem Cells and in Treating Diseases)

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Review

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23 pages, 922 KiB

Open AccessReview

Noncoding RNAs and Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Cardiac Arrhythmic Brugada Syndrome

by Benjamin Theisen, Austin Holtz and Viswanathan Rajagopalan

Cells 2023, 12(19), 2398; https://doi.org/10.3390/cells12192398 - 03 Oct 2023

Cited by 1 | Viewed by 1296

Abstract

Hundreds of thousands of people die each year as a result of sudden cardiac death, and many are due to heart rhythm disorders. One of the major causes of these arrhythmic events is Brugada syndrome, a cardiac channelopathy that results in abnormal cardiac [...] Read more.

Hundreds of thousands of people die each year as a result of sudden cardiac death, and many are due to heart rhythm disorders. One of the major causes of these arrhythmic events is Brugada syndrome, a cardiac channelopathy that results in abnormal cardiac conduction, severe life-threatening arrhythmias, and, on many occasions, death. This disorder has been associated with mutations and dysfunction of about two dozen genes; however, the majority of the patients do not have a definite cause for the diagnosis of Brugada Syndrome. The protein-coding genes represent only a very small fraction of the mammalian genome, and the majority of the noncoding regions of the genome are actively transcribed. Studies have shown that most of the loci associated with electrophysiological traits are located in noncoding regulatory regions and are expected to affect gene expression dosage and cardiac ion channel function. Noncoding RNAs serve an expanding number of regulatory and other functional roles within the cells, including but not limited to transcriptional, post-transcriptional, and epigenetic regulation. The major noncoding RNAs found in Brugada Syndrome include microRNAs; however, others such as long noncoding RNAs are also identified. They contribute to pathogenesis by interacting with ion channels and/or are detectable as clinical biomarkers. Stem cells have received significant attention in the recent past, and can be differentiated into many different cell types including those in the heart. In addition to contractile and relaxational properties, BrS-relevant electrophysiological phenotypes are also demonstrated in cardiomyocytes differentiated from stem cells induced from adult human cells. In this review, we discuss the current understanding of noncoding regions of the genome and their RNA biology in Brugada Syndrome. We also delve into the role of stem cells, especially human induced pluripotent stem cell-derived cardiac differentiated cells, in the investigation of Brugada syndrome in preclinical and clinical studies. Full article

(This article belongs to the Special Issue The Mission of Non-coding RNAs in the Growth and Development of Stem Cells and in Treating Diseases)

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19 pages, 9327 KiB

Open AccessReview

Mesenchymal Stem Cell-Derived Long Noncoding RNAs in Cardiac Injury and Repair

by Talan Tran, Claudia Cruz, Anthony Chan, Salma Awad, Johnson Rajasingh, Richard Deth and Narasimman Gurusamy

Cells 2023, 12(18), 2268; https://doi.org/10.3390/cells12182268 - 13 Sep 2023

Viewed by 1279

Abstract

Cardiac injury, such as myocardial infarction and heart failure, remains a significant global health burden. The limited regenerative capacity of the adult heart poses a challenge for restoring its function after injury. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cardiac [...] Read more.

Cardiac injury, such as myocardial infarction and heart failure, remains a significant global health burden. The limited regenerative capacity of the adult heart poses a challenge for restoring its function after injury. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cardiac regeneration due to their ability to differentiate into various cell types and secrete bioactive molecules. In recent years, attention has been given to noncoding RNAs derived from MSCs, particularly long noncoding RNAs (lncRNAs), and their potential role in cardiac injury and repair. LncRNAs are RNA molecules that do not encode proteins but play critical roles in gene regulation and cellular responses including cardiac repair and regeneration. This review focused on MSC-derived lncRNAs and their implications in cardiac regeneration, including their effects on cardiac function, myocardial remodeling, cardiomyocyte injury, and angiogenesis. Understanding the molecular mechanisms of MSC-derived lncRNAs in cardiac injury and repair may contribute to the development of novel therapeutic strategies for treating cardiovascular diseases. However, further research is needed to fully elucidate the potential of MSC-derived lncRNAs and address the challenges in this field. Full article

(This article belongs to the Special Issue The Mission of Non-coding RNAs in the Growth and Development of Stem Cells and in Treating Diseases)

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28 pages, 2270 KiB

Open AccessReview

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders

by Anurag Mishra, Rishabh Kumar, Satya Narayan Mishra, Sivakumar Vijayaraghavalu, Neeraj Kumar Tiwari, Girish C. Shukla, Narasimman Gurusamy and Munish Kumar

Cells 2023, 12(8), 1159; https://doi.org/10.3390/cells12081159 - 14 Apr 2023

Cited by 3 | Viewed by 1942

Abstract

Stem cells’ self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, [...] Read more.

Stem cells’ self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells’ self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover. Full article

(This article belongs to the Special Issue The Mission of Non-coding RNAs in the Growth and Development of Stem Cells and in Treating Diseases)

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20 pages, 1369 KiB

Open AccessFeature PaperReview

The Mission of Long Non-Coding RNAs in Human Adult Renal Stem/Progenitor Cells and Renal Diseases

by Francesca Giannuzzi, Silvia Maiullari, Loreto Gesualdo and Fabio Sallustio

Cells 2023, 12(8), 1115; https://doi.org/10.3390/cells12081115 - 08 Apr 2023

Cited by 1 | Viewed by 1488

Abstract

Long non-coding RNAs (lncRNAs) are a large, heterogeneous class of transcripts and key regulators of gene expression at both the transcriptional and post-transcriptional levels in different cellular contexts and biological processes. Understanding the potential mechanisms of action of lncRNAs and their role in [...] Read more.

Long non-coding RNAs (lncRNAs) are a large, heterogeneous class of transcripts and key regulators of gene expression at both the transcriptional and post-transcriptional levels in different cellular contexts and biological processes. Understanding the potential mechanisms of action of lncRNAs and their role in disease onset and development may open up new possibilities for therapeutic approaches in the future. LncRNAs also play an important role in renal pathogenesis. However, little is known about lncRNAs that are expressed in the healthy kidney and that are involved in renal cell homeostasis and development, and even less is known about lncRNAs involved in human adult renal stem/progenitor cells (ARPC) homeostasis. Here we give a thorough overview of the biogenesis, degradation, and functions of lncRNAs and highlight our current understanding of their functional roles in kidney diseases. We also discuss how lncRNAs regulate stem cell biology, focusing finally on their role in human adult renal stem/progenitor cells, in which the lncRNA HOTAIR prevents them from becoming senescent and supports these cells to secrete high quantities of α-Klotho, an anti-aging protein capable of influencing the surrounding tissues and therefore modulating the renal aging. Full article

(This article belongs to the Special Issue The Mission of Non-coding RNAs in the Growth and Development of Stem Cells and in Treating Diseases)

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Graphical abstract

24 pages, 2720 KiB

Open AccessReview

Insights on the Biomarker Potential of Exosomal Non-Coding RNAs in Colorectal Cancer: An In Silico Characterization of Related Exosomal lncRNA/circRNA–miRNA–Target Axis

by Maria Mezher, Samira Abdallah, Ohanes Ashekyan, Ayman Al Shoukari, Hayat Choubassy, Abdallah Kurdi, Sally Temraz and Rihab Nasr

Cells 2023, 12(7), 1081; https://doi.org/10.3390/cells12071081 - 04 Apr 2023

Cited by 4 | Viewed by 2762

Abstract

Colorectal cancer (CRC) is one of the most common cancer types, ranking third after lung and breast cancers. As such, it demands special attention for better characterization, which may eventually result in the development of early detection strategies and preventive measures. Currently, components [...] Read more.

Colorectal cancer (CRC) is one of the most common cancer types, ranking third after lung and breast cancers. As such, it demands special attention for better characterization, which may eventually result in the development of early detection strategies and preventive measures. Currently, components of bodily fluids, which may reflect various disease states, are being increasingly researched for their biomarker potential. One of these components is the circulating extracellular vesicles, namely, exosomes, which are demonstrated to carry various cargo. Of importance, the non-coding RNA cargo of circulating exosomes, especially long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and micro RNAs (miRNAs), may potentially serve as significant diagnostic and prognostic/predictive biomarkers. In this review, we present existing evidence on the diagnostic and prognostic/predictive biomarker value of exosomal non-coding RNAs in CRC. In addition, taking advantage of the miRNA sponging functionality of lncRNAs and circRNAs, we demonstrate an experimentally validated CRC exosomal non-coding RNA-regulated target gene axis benefiting from published miRNA sponging studies in CRC. Hence, we present a set of target genes and pathways downstream of the lncRNA/circRNA–miRNA–target axis along with associated significant Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may collectively serve to better characterize CRC and shed light on the significance of exosomal non-coding RNAs in CRC diagnosis and prognosis/prediction. Full article

(This article belongs to the Special Issue The Mission of Non-coding RNAs in the Growth and Development of Stem Cells and in Treating Diseases)

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28 pages, 2435 KiB

Open AccessFeature PaperReview

Influence of Long Non-Coding RNA in the Regulation of Cancer Stem Cell Signaling Pathways

by Kevina Sonawala, Satish Ramalingam and Iyappan Sellamuthu

Cells 2022, 11(21), 3492; https://doi.org/10.3390/cells11213492 - 04 Nov 2022

Cited by 6 | Viewed by 2618

Abstract

Over the past two decades, cancer stem cells (CSCs) have emerged as an immensely studied and experimental topic, however a wide range of questions concerning the topic still remain unanswered; in particular, the mechanisms underlying the regulation of tumor stem cells and their [...] Read more.

Over the past two decades, cancer stem cells (CSCs) have emerged as an immensely studied and experimental topic, however a wide range of questions concerning the topic still remain unanswered; in particular, the mechanisms underlying the regulation of tumor stem cells and their characteristics. Understanding the cancer stem-cell signaling pathways may pave the way towards a better comprehension of these mechanisms. Signaling pathways such as WNT, STAT, Hedgehog, NOTCH, PI3K/AKT/mTOR, TGF-β, and NF-κB are responsible not only for modulating various features of CSCs but also their microenvironments. Recently, the prominent roles of various non-coding RNAs such as small non-coding RNAs (sncRNAs) and long non-coding RNAs (lncRNAs) in developing and enhancing the tumor phenotypes have been unfolded. This review attempts to shed light on understanding the influence of long non- coding RNAs in the modulation of various CSC-signaling pathways and its impact on the CSCs and tumor properties; highlighting the protagonistic and antagonistic roles of lncRNAs. Full article

(This article belongs to the Special Issue The Mission of Non-coding RNAs in the Growth and Development of Stem Cells and in Treating Diseases)

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