International Journal of Molecular Sciences

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14 pages, 2260 KiB

Open AccessArticle

Synergic Action of Insulin-like Growth Factor-2 and miRNA-483 in Pterygium Pathogenesis

by Cristina Maxia, Michela Isola, Eleonora Grecu, Alberto Cuccu, Alessandra Scano, Germano Orrù, Nick Di Girolamo, Andrea Diana and Daniela Murtas

Int. J. Mol. Sci. 2023, 24(5), 4329; https://doi.org/10.3390/ijms24054329 - 22 Feb 2023

Cited by 4 | Viewed by 1612

Abstract

Pterygium is a multifactorial disease in which UV-B is speculated to play a key role by inducing oxidative stress and phototoxic DNA damage. In search for candidate molecules that are useful for justifying the intense epithelial proliferation observed in pterygium, our attention has [...] Read more.

Pterygium is a multifactorial disease in which UV-B is speculated to play a key role by inducing oxidative stress and phototoxic DNA damage. In search for candidate molecules that are useful for justifying the intense epithelial proliferation observed in pterygium, our attention has been focused on Insulin-like Growth Factor 2 (IGF-2), mainly detected in embryonic and fetal somatic tissues, which regulate metabolic and mitogenic functions. The binding between IGF-2 and its receptor Insulin-like Growth Factor 1 Receptor (IGF-1R) activates the PI3K-AKT pathway, which leads to the regulation of cell growth, differentiation, and the expression of specific genes. Since IGF2 is regulated by parental imprinting, in different human tumors, the IGF2 Loss of Imprinting (LOI) results in IGF-2- and IGF2-derived intronic miR-483 overexpression. Based on these activities, the purpose of this study was to investigate the overexpression of IGF-2, IGF-1R, and miR-483. Using an immunohistochemical approach, we demonstrated an intense colocalized epithelial overexpression of IGF-2 and IGF-1R in most pterygium samples (Fisher’s exact test, p = 0.021). RT-qPCR gene expression analysis confirmed IGF2 upregulation and demonstrated miR-483 expression in pterygium compared to normal conjunctiva (253.2-fold and 12.47-fold, respectively). Therefore, IGF-2/IGF-1R co-expression could suggest their interplay through the two different paracrine/autocrine IGF-2 routes for signaling transfer, which would activate the PI3K/AKT signaling pathway. In this scenario, miR-483 gene family transcription might synergically reinforce IGF-2 oncogenic function through its boosting pro-proliferative and antiapoptotic activity. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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16 pages, 5022 KiB

Open AccessArticle

circINSR Inhibits Adipogenic Differentiation of Adipose-Derived Stromal Vascular Fractions through the miR-152/MEOX2 Axis in Sheep

by Bishi Zhao, Hanyue Zhang, Dan Zhao, Yu Liang, Liying Qiao, Jianhua Liu, Yangyang Pan, Kaijie Yang and Wenzhong Liu

Int. J. Mol. Sci. 2023, 24(4), 3501; https://doi.org/10.3390/ijms24043501 - 09 Feb 2023

Viewed by 1335

Abstract

Adipose tissue plays a crucial role in energy metabolism. Several studies have shown that circular RNA (circRNA) is involved in the regulation of fat development and lipid metabolism. However, little is known about their involvement in the adipogenic differentiation of ovine stromal vascular [...] Read more.

Adipose tissue plays a crucial role in energy metabolism. Several studies have shown that circular RNA (circRNA) is involved in the regulation of fat development and lipid metabolism. However, little is known about their involvement in the adipogenic differentiation of ovine stromal vascular fractions (SVFs). Here, based on previous sequencing data and bioinformatics analysis, a novel circINSR was identified in sheep, which acts as a sponge to promote miR-152 in inhibiting the adipogenic differentiation of ovine SVFs. The interactions between circINSR and miR-152 were examined using bioinformatics, luciferase assays, and RNA immunoprecipitation. Of note, we found that circINSR was involved in adipogenic differentiation via the miR-152/mesenchyme homeobox 2 (MEOX2) pathway. MEOX2 inhibited adipogenic differentiation of ovine SVFs and miR-152 inhibited the expression of MEOX2. In other words, circINSR directly isolates miR-152 in the cytoplasm and inhibits its ability to promote adipogenic differentiation of ovine SVFs. In summary, this study revealed the role of circINSR in the adipogenic differentiation of ovine SVFs and its regulatory mechanisms, providing a reference for further interpretation of the development of ovine fat and its regulatory mechanisms. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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18 pages, 17686 KiB

Open AccessArticle

LncRNA WDR11-AS1 Promotes Extracellular Matrix Synthesis in Osteoarthritis by Directly Interacting with RNA-Binding Protein PABPC1 to Stabilize SOX9 Expression

by Huang Huang, Jidong Yan, Xi Lan, Yuanxu Guo, Mengyao Sun, Yitong Zhao, Fujun Zhang, Jian Sun and Shemin Lu

Int. J. Mol. Sci. 2023, 24(1), 817; https://doi.org/10.3390/ijms24010817 - 03 Jan 2023

Cited by 5 | Viewed by 1994

Abstract

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, [...] Read more.

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as SOX9, and the inhibition of PABPC1 improved the mRNA stability of SOX9 to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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12 pages, 1015 KiB

Open AccessArticle

Hepato-Protective Effects of Delta-Tocotrienol and Alpha-Tocopherol in Patients with Non-Alcoholic Fatty Liver Disease: Regulation of Circulating MicroRNA Expression

by Muhammad Amjad Pervez, Dilshad Ahmed Khan, Sayed Tanveer Abbas Gilani, Safia Fatima, Aamir Ijaz and Sumbal Nida

Int. J. Mol. Sci. 2023, 24(1), 79; https://doi.org/10.3390/ijms24010079 - 21 Dec 2022

Cited by 5 | Viewed by 2315

Abstract

MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in [...] Read more.

MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 (n = 50) 300 mg or αTF (n = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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20 pages, 3850 KiB

Open AccessArticle

LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP Pathway

by Yong Wang, Yunxia Guo, Chunhui Duan, Junjie Li, Shoukun Ji, Huihui Yan, Yueqin Liu and Yingjie Zhang

Int. J. Mol. Sci. 2022, 23(20), 12132; https://doi.org/10.3390/ijms232012132 - 12 Oct 2022

Cited by 2 | Viewed by 1349

Abstract

Long non-coding RNAs (lncRNAs) have been shown to play important roles in livestock fecundity, and many lncRNAs that affect follicular development and reproductive diseases have been identified in the ovary. However, only a few of them have been functionally annotated and mechanistically validated. [...] Read more.

Long non-coding RNAs (lncRNAs) have been shown to play important roles in livestock fecundity, and many lncRNAs that affect follicular development and reproductive diseases have been identified in the ovary. However, only a few of them have been functionally annotated and mechanistically validated. In this study, we identified a new lncRNA (lncGSAR) and investigated its effects on the proliferation and steroidogenesis of ovine granulosa cells (GCs). High concentrations of glucose (add 33.6 mM glucose) caused high expression of lncGSAR in GCs by regulating its stability, and lncGSAR overexpression promoted GCs proliferation, estrogen secretion, and inhibited progesterone secretion, whereas interference with lncGASR had the opposite effect. Next, we found that the RNA molecules of lncGSAR act on MiR-125b as competitive endogenous RNA (ceRNA), and SREBP-cleavage-activating protein (SCAP) was verified as a target of MiR-125b. LncGASR overexpression increased the expression of SCAP, SREBP, and steroid hormone-related proteins, which can be attenuated by MiR-125b. Our results demonstrated that lncGSAR can act as a ceRNA to activate SCAP/SREBP signaling by sponging MiR-125b to regulate steroid hormone secretion in GCs. These findings provide new insights into the mechanisms of nutrient-regulated follicle development in ewes. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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18 pages, 2728 KiB

Open AccessArticle

Differential Expression of miRNAs and Their Predicted Target Genes Indicates That Gene Expression in Atlantic Salmon Gill Is Post-Transcriptionally Regulated by miRNAs in the Parr-Smolt Transformation and Adaptation to Sea Water

by Alice Shwe, Aleksei Krasnov, Tina Visnovska, Sigmund Ramberg, Tone-Kari K. Østbye and Rune Andreassen

Int. J. Mol. Sci. 2022, 23(15), 8831; https://doi.org/10.3390/ijms23158831 - 08 Aug 2022

Cited by 4 | Viewed by 2508

Abstract

Smoltification (parr-smolt transformation) is a complex developmental process consisting of developmental changes that lead to remodeling of the Atlantic salmon gill. Here, the expression changes of miRNAs and mRNAs were studied by small-RNA sequencing and microarray analysis, respectively, to identify miRNAs and their [...] Read more.

Smoltification (parr-smolt transformation) is a complex developmental process consisting of developmental changes that lead to remodeling of the Atlantic salmon gill. Here, the expression changes of miRNAs and mRNAs were studied by small-RNA sequencing and microarray analysis, respectively, to identify miRNAs and their predicted targets associated with smoltification and subsequent sea water adaptation (SWA). In total, 18 guide miRNAs were identified as differentially expressed (gDE miRNAs). Hierarchical clustering analysis of expression changes divided these into one cluster of 13 gDE miRNAs with decreasing expression during smoltification and SWA that included the miRNA-146, miRNA-30 and miRNA-7132 families. Another smaller cluster that showed increasing expression consisted of miR-101a-3p, miR-193b-5p, miR-499a-5p, miR-727a-3p and miR-8159-5p. The gDE miRNAs were predicted to target 747 of the genes (DE mRNAs), showing expression changes in the microarray analysis. The predicted targets included genes encoding NKA-subunits, aquaporin-subunits, cystic fibrosis transmembrane conductance regulator and the solute carrier family. Furthermore, the predicted target genes were enriched in biological processes associated with smoltification and SWA (e.g., immune system, reactive oxygen species, stress response and extracellular matrix organization). Collectively, the results indicate that remodeling of the gill involves the post-transcriptional regulation of gene expression by the characterized gDE miRNAs. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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18 pages, 3191 KiB

Open AccessArticle

miR-143-3p Inhibits Aberrant Tau Phosphorylation and Amyloidogenic Processing of APP by Directly Targeting DAPK1 in Alzheimer’s Disease

by Long Wang, Xindong Shui, Yingxue Mei, Yongfang Xia, Guihua Lan, Li Hu, Mi Zhang, Chen-Ling Gan, Ruomeng Li, Yuan Tian, Quling Wang, Xi Gu, Dongmei Chen, Tao Zhang and Tae Ho Lee

Int. J. Mol. Sci. 2022, 23(14), 7992; https://doi.org/10.3390/ijms23147992 - 20 Jul 2022

Cited by 18 | Viewed by 2102

Abstract

The neuropathology of Alzheimer’s disease (AD) is characterized by intracellular aggregation of hyperphosphorylated tau and extracellular accumulation of beta-amyloid (Aβ). Death-associated protein kinase 1 (DAPK1), as a novel therapeutic target, shows promise for the treatment of human AD, but the regulatory mechanisms of [...] Read more.

The neuropathology of Alzheimer’s disease (AD) is characterized by intracellular aggregation of hyperphosphorylated tau and extracellular accumulation of beta-amyloid (Aβ). Death-associated protein kinase 1 (DAPK1), as a novel therapeutic target, shows promise for the treatment of human AD, but the regulatory mechanisms of DAPK1 expression in AD remain unclear. In this study, we identified miR-143-3p as a promising candidate for targeting DAPK1. miR-143-3p directly bound to the 3′ untranslated region of human DAPK1 mRNA and inhibited its translation. miR-143-3p decreased tau phosphorylation and promoted neurite outgrowth and microtubule assembly. Moreover, miR-143-3p attenuated amyloid precursor protein (APP) phosphorylation and reduced the generation of Aβ40 and Aβ42. Furthermore, restoring DAPK1 expression with miR-143-3p antagonized the effects of miR-143-3p in attenuating tau hyperphosphorylation and Aβ production. In addition, the miR-143-3p levels were downregulated and correlated inversely with the expression of DAPK1 in the hippocampus of AD patients. Our results suggest that miR-143-3p might play critical roles in regulating both aberrant tau phosphorylation and amyloidogenic processing of APP by targeting DAPK1 and thus offer a potential novel therapeutic strategy for AD. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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28 pages, 4884 KiB

Open AccessArticle

miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly

by Merit Wildung, Christian Herr, Dietmar Riedel, Cornelia Wiedwald, Alena Moiseenko, Fidel Ramírez, Hataitip Tasena, Maren Heimerl, Mihai Alevra, Naira Movsisyan, Maike Schuldt, Larisa Volceanov-Hahn, Sharen Provoost, Tabea Nöthe-Menchen, Diana Urrego, Bernard Freytag, Julia Wallmeier, Christoph Beisswenger, Robert Bals, Maarten van den Berge, Wim Timens, Pieter S. Hiemstra, Corry-Anke Brandsma, Tania Maes, Stefan Andreas, Irene H. Heijink, Luis A. Pardo and Muriel Lizé Show full author list Hide full author list

Int. J. Mol. Sci. 2022, 23(14), 7749; https://doi.org/10.3390/ijms23147749 - 13 Jul 2022

Cited by 1 | Viewed by 2754

Abstract

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 [...] Read more.

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449^−/− mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449^−/− mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449^−/− mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449^−/− cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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20 pages, 4342 KiB

Open AccessArticle

Long Non-Coding RNA GDAR Regulates Ovine Granulosa Cells Apoptosis by Affecting the Expression of Apoptosis-Related Genes

by Yong Wang, Yunxia Guo, Chunhui Duan, Ruochen Yang, Lechao Zhang, Yueqin Liu and Yingjie Zhang

Int. J. Mol. Sci. 2022, 23(9), 5183; https://doi.org/10.3390/ijms23095183 - 06 May 2022

Cited by 5 | Viewed by 1597

Abstract

Short-term dietary supplementation of ewes during the luteal phase can increase fertility, most probably by stimulating glucose uptake by the follicles. However, the molecular mechanism of glucose regulation of follicular development has not yet been clarified, especially the further study of long non-coding [...] Read more.

Short-term dietary supplementation of ewes during the luteal phase can increase fertility, most probably by stimulating glucose uptake by the follicles. However, the molecular mechanism of glucose regulation of follicular development has not yet been clarified, especially the further study of long non-coding RNA (lncRNA) in determining fertility during follicular development. We generated granulosa cell (GC) models of different doses of glucose (0, 2.1, 4.2, 8.4, 16.8 and 33.6 mM), and observed that the highest cell viability was recorded in the 8.4 mM group and the highest apoptosis rates were recorded in the 33.6 mM group. Therefore, a control group (n = 3, 0 mM glucose), a low glucose group (n = 3, add 8.4 mM glucose), and a high glucose group (n = 3, add 33.6 mM glucose) of GCs were created for next whole genomic RNA sequencing. In total, 18,172 novel lncRNAs and 510 annotated lncRNAs were identified in the GCs samples. Gene Ontology indicated that differentially expressed lncRNAs associated with cell apoptosis were highly enriched. Kyoto Encyclopedia of Genes and Genomes enrichment analysis of lncRNA target genes found that the apoptosis pathway and the p53 signaling pathway were both enriched. Furthermore, we focused on the function of a lncGDAR and verified that lncGDAR could influence cell apoptosis in GC development through affecting the mRNA and protein expression of apoptosis-related markers. These results provide the basis for further study of the lncRNA regulation mechanism in nutrition on female fertility. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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20 pages, 3633 KiB

Open AccessArticle

Long Non-Coding RNA LINC02802 Regulates In Vitro Sprouting Angiogenesis by Sponging microRNA-486-5p

by Stefania Rosano, Sushant Parab, Alessio Noghero, Davide Corà and Federico Bussolino

Int. J. Mol. Sci. 2022, 23(3), 1653; https://doi.org/10.3390/ijms23031653 - 31 Jan 2022

Cited by 3 | Viewed by 2709

Abstract

In the last several years, accumulating evidence indicates that noncoding RNAs, especially long-noncoding RNAs (lncRNAs) and microRNAs, play essential roles in regulating angiogenesis. However, the contribution of lncRNA-mediated competing-endogenous RNA (ceRNA) activity in the control of capillary sprouting from the pre-existing ones has [...] Read more.

In the last several years, accumulating evidence indicates that noncoding RNAs, especially long-noncoding RNAs (lncRNAs) and microRNAs, play essential roles in regulating angiogenesis. However, the contribution of lncRNA-mediated competing-endogenous RNA (ceRNA) activity in the control of capillary sprouting from the pre-existing ones has not been described so far. Here, by exploiting the transcriptomic profile of VEGF-A-activated endothelial cells in a consolidate three-dimensional culture system, we identified a list of lncRNAs whose expression was modified during the sprouting process. By crossing the lncRNAs with a higher expression level and the highest fold change value between unstimulated and VEGF-A-stimulated endothelial cells, we identified the unknown LINC02802 as the best candidate to take part in sprouting regulation. LINC02802 was upregulated after VEGF-A stimulation and its knockdown resulted in a significant reduction in sprouting activity. Mechanistically, we demonstrated that LINC02802 acts as a ceRNA in the post-transcriptional regulation of Mastermind-like-3 (MAML3) gene expression through a competitive binding with miR-486-5p. Taken together, these results suggest that LINC02802 plays a critical role in preventing the miR-486-5p anti-angiogenic effect and that this inhibitory effect results from the reduction in MAML3 expression. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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Review

Jump to: Research

27 pages, 1984 KiB

Open AccessReview

Non-Coding RNAs Regulating Mitochondrial Functions and the Oxidative Stress Response as Putative Targets against Age-Related Macular Degeneration (AMD)

by Juha M. T. Hyttinen, Janusz Blasiak and Kai Kaarniranta

Int. J. Mol. Sci. 2023, 24(3), 2636; https://doi.org/10.3390/ijms24032636 - 30 Jan 2023

Cited by 8 | Viewed by 2016

Abstract

Age-related macular degeneration (AMD) is an ever-increasing, insidious disease which reduces the quality of life of millions of elderly people around the world. AMD is characterised by damage to the retinal pigment epithelium (RPE) in the macula region of the retina. The origins [...] Read more.

Age-related macular degeneration (AMD) is an ever-increasing, insidious disease which reduces the quality of life of millions of elderly people around the world. AMD is characterised by damage to the retinal pigment epithelium (RPE) in the macula region of the retina. The origins of this multi-factorial disease are complex and still not fully understood. Oxidative stress and mitochondrial imbalance in the RPE are believed to be important factors in the development of AMD. In this review, the regulation of the mitochondrial function and antioxidant stress response by non-coding RNAs (ncRNAs), newly emerged epigenetic factors, is discussed. These molecules include microRNAs, long non-coding RNAs, and circular non-coding RNAs. They act mainly as mRNA suppressors, controllers of other ncRNAs, or by interacting with proteins. We include here examples of these RNA molecules which affect various mitochondrial processes and antioxidant signaling of the cell. As a future prospect, the possibility to manipulate these ncRNAs to strengthen mitochondrial and antioxidant response functions is discussed. Non-coding RNAs could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, either by suppressing or increasing their expression. In addition to AMD, it is possible that non-coding RNAs could be regulators in other oxidative stress-related degenerative diseases. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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16 pages, 706 KiB

Open AccessReview

Neuronal and Glial Communication via Non-Coding RNAs: Messages in Extracellular Vesicles

by Davide Marangon, Juliana Helena Castro e Silva and Davide Lecca

Int. J. Mol. Sci. 2023, 24(1), 470; https://doi.org/10.3390/ijms24010470 - 28 Dec 2022

Cited by 2 | Viewed by 2545

Abstract

Extracellular vesicles (EVs) have been increasingly recognized as essential players in cell communication in many organs and systems, including the central nervous system (CNS). A proper interaction between neural cells is fundamental in the regulation of neurophysiological processes and its alteration could induce [...] Read more.

Extracellular vesicles (EVs) have been increasingly recognized as essential players in cell communication in many organs and systems, including the central nervous system (CNS). A proper interaction between neural cells is fundamental in the regulation of neurophysiological processes and its alteration could induce several pathological phenomena, such as neurodegeneration, neuroinflammation, and demyelination. EVs contain and transfer complex molecular cargoes typical of their cells of origin, such as proteins, lipids, carbohydrates, and metabolites to recipient cells. EVs are also enriched in non-coding RNAs (e.g., microRNAs, lncRNAs, and circRNA), which were formerly considered as cell-intrinsic regulators of CNS functions and pathologies, thus representing a new layer of regulation in the cell-to-cell communication. In this review, we summarize the most recent and advanced studies on the role of EV-derived ncRNAs in the CNS. First, we report the potential of neural stem cell-derived ncRNAs as new therapeutic tools for neurorepair. Then, we discuss the role of neuronal ncRNAs in regulating glia activation, and how alteration in glial ncRNAs influences neuronal survival and synaptic functions. We conclude that EV-derived ncRNAs can act as intercellular signals in the CNS to either propagate neuroinflammatory waves or promote reparative functions. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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60 pages, 1398 KiB

Open AccessReview

Micro-Players of Great Significance—Host microRNA Signature in Viral Infections in Humans and Animals

by Ewa Ostrycharz and Beata Hukowska-Szematowicz

Int. J. Mol. Sci. 2022, 23(18), 10536; https://doi.org/10.3390/ijms231810536 - 11 Sep 2022

Cited by 9 | Viewed by 4842

Abstract

Over time, more and more is becoming known about micro-players of great significance. This is particularly the case for microRNAs (miRNAs; miR), which have been found to participate in the regulation of many physiological and pathological processes in both humans and animals. One [...] Read more.

Over time, more and more is becoming known about micro-players of great significance. This is particularly the case for microRNAs (miRNAs; miR), which have been found to participate in the regulation of many physiological and pathological processes in both humans and animals. One such process is viral infection in humans and animals, in which the host miRNAs—alone or in conjunction with the virus—interact on two levels: viruses may regulate the host’s miRNAs to evade its immune system, while the host miRNAs can play anti- or pro-viral roles. The purpose of this comprehensive review is to present the key miRNAs involved in viral infections in humans and animals. We summarize the data in the available literature, indicating that the signature miRNAs in human viral infections mainly include 12 miRNAs (i.e., miR-155, miR-223, miR-146a, miR-122, miR-125b, miR-132, miR-34a, miR -21, miR-16, miR-181 family, let-7 family, and miR-10a), while 10 miRNAs are commonly found in animals (i.e., miR-155, miR-223, miR-146a, miR-145, miR-21, miR-15a/miR-16 cluster, miR-181 family, let-7 family, and miR-122) in this context. Knowledge of which miRNAs are involved in different viral infections and the biological functions that they play can help in understanding the pathogenesis of viral diseases, facilitating the future development of therapeutic agents for both humans and animals. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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24 pages, 1039 KiB

Open AccessReview

MiR-155: An Important Regulator of Neuroinflammation

by Valeria Domenica Zingale, Agnese Gugliandolo and Emanuela Mazzon

Int. J. Mol. Sci. 2022, 23(1), 90; https://doi.org/10.3390/ijms23010090 - 22 Dec 2021

Cited by 52 | Viewed by 4044

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and that play an important role in many cellular processes, including modulation of inflammation. MiRNAs are present in high concentrations in the central nervous system (CNS) and are [...] Read more.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and that play an important role in many cellular processes, including modulation of inflammation. MiRNAs are present in high concentrations in the central nervous system (CNS) and are spatially and temporally expressed in a specific way. Therefore, an imbalance in the expression pattern of these small molecules can be involved in the development of neurological diseases. Generally, CNS responds to damage or disease through the activation of an inflammatory response, but many neurological disorders are characterized by uncontrolled neuroinflammation. Many studies support the involvement of miRNAs in the activation or inhibition of inflammatory signaling and in the promotion of uncontrolled neuroinflammation with pathological consequences. MiR-155 is a pro-inflammatory mediator of the CNS and plays an important regulatory role. The purpose of this review is to summarize how miR-155 is regulated and the pathological consequences of its deregulation during neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease and other neuroinflammatory disorders. Modulation of miRNAs’ expression could be used as a therapeutic strategy in the treatment of pathological neuroinflammation. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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15 pages, 667 KiB

Open AccessReview

The Study of Cerebrospinal Fluid microRNAs in Spinal Cord Injury and Neurodegenerative Diseases: Methodological Problems and Possible Solutions

by Irina Baichurina, Victor Valiullin, Victoria James, Albert Rizvanov and Yana Mukhamedshina

Int. J. Mol. Sci. 2022, 23(1), 114; https://doi.org/10.3390/ijms23010114 - 22 Dec 2021

Cited by 6 | Viewed by 2995

Abstract

Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal [...] Read more.

Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal cord injury (SCI) and neurodegenerative diseases. It is believed that the changes in gene expression associated with processes triggered by neurological disorders are the result of post-transcriptional gene regulation. microRNAs (miRNAs) are key regulators of post-transcriptional gene expression and, as such, are often looked to in the search for effective biomarkers. We propose that cerebrospinal fluid (CSF) is potentially a source of biomarkers since it is in direct contact with the central nervous system and therefore may contain biomarkers indicating neurodegeneration or damage to the brain and spinal cord. However, since the abundance of miRNAs in CSF is low, their isolation and detection is technically difficult. In this review, we evaluate the findings of recent studies of CSF miRNAs as biomarkers of spinal cord injury (SCI) and neurodegenerative diseases. We also summarize the current knowledge concerning the methods of studying miRNA in CSF, including RNA isolation and normalization of the data, highlighting the caveats of these approaches and possible solutions. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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11 pages, 636 KiB

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Nucleolar Proteins and Non-Coding RNAs: Roles in Renal Cancer

by Piotr Popławski, Joanna Bogusławska, Karolina Hanusek and Agnieszka Piekiełko-Witkowska

Int. J. Mol. Sci. 2021, 22(23), 13126; https://doi.org/10.3390/ijms222313126 - 04 Dec 2021

Cited by 9 | Viewed by 2293

Abstract

Renal cell cancer is the most frequent kidney malignancy. Most RCC cases are classified as clear cell renal cell carcinoma (ccRCC), characterized by high aggressiveness and poor prognosis for patients. ccRCC aggressiveness is defined by classification systems based on changes in morphology of [...] Read more.

Renal cell cancer is the most frequent kidney malignancy. Most RCC cases are classified as clear cell renal cell carcinoma (ccRCC), characterized by high aggressiveness and poor prognosis for patients. ccRCC aggressiveness is defined by classification systems based on changes in morphology of nucleoli, the membraneless substructures of nuclei. The latter act as the sites of ribosome biogenesis as well as the hubs that trap and immobilize proteins, preventing their action in other cellular compartments. Thereby, nucleoli control cellular functioning and homeostasis. Nucleoli are also the sites of activity of multiple noncoding RNAs, including snoRNAs, IGS RNA, and miRNAs. Recent years have brought several remarkable discoveries regarding the role of nucleolar non-coding RNAs, in particular snoRNAs, in ccRCC. The expression of snoRNAs is largely dysregulated in ccRCC tumors. snoRNAs, such as SNHG1, SNHG4 and SNHG12, act as miRNA sponges, leading to aberrant expression of oncogenes and tumor suppressors, and directly contributing to ccRCC development and progression. snoRNAs can also act without affecting miRNA functioning, by altering the expression of key oncogenic proteins such as HIF1A. snoRNAs are also potentially useful biomarkers of ccRCC progression. Here, we comprehensively discuss the role of nucleolar proteins and non-coding RNAs in ccRCC. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

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