miRNAs in Pathophysiology of Disease

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19 pages, 1010 KiB

Open AccessReview

Exploring microRNA-Mediated Immune Responses to Soil-Transmitted Helminth and Herpes Simplex Virus Type 2 Co-Infections

by Roxanne Pillay, Pragalathan Naidoo and Zilungile L. Mkhize-Kwitshana

Diseases 2025, 13(1), 6; https://doi.org/10.3390/diseases13010006 - 1 Jan 2025

Viewed by 1167

Abstract

Over the last two decades, the field of microRNA (miRNA) research has grown significantly. MiRNAs are a class of short, single-stranded, non-coding RNAs that regulate gene expression post-transcriptionally. Thereby, miRNAs regulate various essential biological processes including immunity. Dysregulated miRNAs are associated with various infectious and non-infectious diseases. Recently co-infection with soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2) has become a focus of study. Both pathogens can profoundly influence host immunity, particularly in under-resourced and co-endemic regions. It is well known that STHs induce immunomodulatory responses that have bystander effects on unrelated conditions. Typically, STHs induce T-helper 2 (Th2) and immunomodulatory responses, which may dampen the proinflammatory T-helper 1 (Th1) immune responses triggered by HSV-2. However, the extent to which STH co-infection influences the host immune response to HSV-2 is not well understood. Moreover, little is known about how miRNAs shape the immune response to STH/HSV-2 co-infection. In this article, we explore the potential influence that STH co-infection may have on host immunity to HSV-2. Because STH and HSV-2 infections are widespread and disproportionately affect vulnerable and impoverished countries, it is important to consider how STHs may impact HSV-2 immunity. Specifically, we explore how miRNAs contribute to both helminth and HSV-2 infections and discuss how miRNAs may mediate STH/HSV-2 co-infections. Insight into miRNA-mediated immune responses may further improve our understanding of the potential impact of STH/HSV-2 co-infections. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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16 pages, 4231 KiB

Open AccessArticle

In Silico Identification of Dysregulated miRNAs Targeting KRAS Gene in Pancreatic Cancer

by Asbiel Felipe Garibaldi-Ríos, Luis E. Figuera, Guillermo Moisés Zúñiga-González, Belinda Claudia Gómez-Meda, Patricia Montserrat García-Verdín, Irving Alejandro Carrillo-Dávila, Itzae Adonai Gutiérrez-Hurtado, Blanca Miriam Torres-Mendoza and Martha Patricia Gallegos-Arreola

Diseases 2024, 12(7), 152; https://doi.org/10.3390/diseases12070152 - 12 Jul 2024

Cited by 2 | Viewed by 1730

Abstract

Pancreatic cancer (PC) is highly lethal, with KRAS mutations in up to 95% of cases. miRNAs inversely correlate with KRAS expression, indicating potential as biomarkers. This study identified miRNAs targeting KRAS and their impact on PC characteristics using in silico methods. dbDEMC identified dysregulated miRNAs in PC; TargetScan, miRDB, and PolymiRTS 3.0 identified miRNAs specific for the KRAS gene; and OncomiR evaluated the association of miRNAs with clinical characteristics and survival in PC. The correlation between miRNAs and KRAS was analysed using ENCORI/starBase. A total of 210 deregulated miRNAs were identified in PC (116 overexpressed and 94 underexpressed). In total, 16 of them were involved in the regulation of KRAS expression and 9 of these (hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30b-5p, hsa-miR-30e-5p, hsa-miR-377-3p, hsa-miR-495-3p, hsa-miR-654-3p, hsa-miR-877-5p and hsa-miR-885-5p) were associated with the clinical characteristics of the PC. Specifically, the overexpression of hsa-miR-30a-5p was associated with PC mortality, and hsa-miR-30b-5p, hsa-miR-377-3p, hsa-miR-495-3p, and hsa-miR-885-5p were associated with survival. Correlation analysis revealed that the expression of 10 miRNAs is correlated with KRAS expression. The dysregulated miRNAs identified in PC may regulate KRAS and some are associated with clinically relevant features, highlighting their potential as biomarkers and therapeutic targets in PC treatment. However, experimental validation is required for confirmation. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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29 pages, 3008 KiB

Open AccessReview

The Involvement of microRNAs in Bone Remodeling Signaling Pathways and Their Role in the Development of Osteoporosis

by Rogelio F. Jiménez-Ortega, Alejandra I. Ortega-Meléndez, Nelly Patiño, Berenice Rivera-Paredez, Alberto Hidalgo-Bravo and Rafael Velázquez-Cruz

Biology 2024, 13(7), 505; https://doi.org/10.3390/biology13070505 - 7 Jul 2024

Cited by 8 | Viewed by 3320

Abstract

Bone remodeling, crucial for maintaining the balance between bone resorption and formation, relies on the coordinated activity of osteoclasts and osteoblasts. During osteoclastogenesis, hematopoietic stem cells (HSCs) differentiate into the osteoclast lineage through the signaling pathways OPG/RANK/RANKL. On the other hand, during osteoblastogenesis, mesenchymal stem cells (MSCs) differentiate into the osteoblast lineage through activation of the signaling pathways TGF-β/BMP/Wnt. Recent studies have shown that bone remodeling is regulated by post-transcriptional mechanisms including microRNAs (miRNAs). miRNAs are small, single-stranded, noncoding RNAs approximately 22 nucleotides in length. miRNAs can regulate virtually all cellular processes through binding to miRNA-response elements (MRE) at the 3’ untranslated region (3′UTR) of the target mRNA. miRNAs are involved in controlling gene expression during osteogenic differentiation through the regulation of key signaling cascades during bone formation and resorption. Alterations of miRNA expression could favor the development of bone disorders, including osteoporosis. This review provides a general description of the miRNAs involved in bone remodeling and their significance in osteoporosis development. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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19 pages, 382 KiB

Open AccessReview

MicroRNAs in Juvenile Idiopathic Arthritis: State of the Art and Future Perspectives

by Simone Pelassa, Federica Raggi, Chiara Rossi and Maria Carla Bosco

Biology 2023, 12(7), 991; https://doi.org/10.3390/biology12070991 - 12 Jul 2023

Cited by 1 | Viewed by 1852

Abstract

Juvenile Idiopathic Arthritis (JIA) represents the most common chronic pediatric arthritis in Western countries and a leading cause of disability in children. Despite recent clinical achievements, patient management is still hindered by a lack of diagnostic/prognostic biomarkers and targeted treatment protocols. MicroRNAs (miRNAs) are short non-coding RNAs playing a key role in gene regulation, and their involvement in many pathologies has been widely reported in the literature. In recent decades, miRNA’s contribution to the regulation of the immune system and the pathogenesis of autoimmune diseases has been demonstrated. Furthermore, miRNAs isolated from patients’ biological samples are currently under investigation for their potential as novel biomarkers. This review aims to provide an overview of the state of the art on miRNA investigation in JIA. The literature addressing the expression of miRNAs in different types of biological samples isolated from JIA patients was reviewed, focusing in particular on their potential application as diagnostic/prognostic biomarkers. The role of miRNAs in the regulation of immune responses in affected joints will also be discussed along with their potential utility as markers of patients’ responses to therapeutic approaches. This information will be of value to investigators in the field of pediatric rheumatology, encouraging further research to increase our knowledge of miRNAs’ potential for future clinical applications in JIA. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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21 pages, 2697 KiB

Open AccessArticle

MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPARα and TIMP2

by Suryakant Niture, Sashi Gadi, Qi Qi, Maxwell Afari Gyamfi, Rency S. Varghese, Leslimar Rios-Colon, Uchechukwu Chimeh, Vandana, Habtom W. Ressom and Deepak Kumar

Cancers 2023, 15(6), 1715; https://doi.org/10.3390/cancers15061715 - 10 Mar 2023

Cited by 14 | Viewed by 3128

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that bind with the 3′ untranslated regions (UTRs) of genes to regulate expression. Downregulation of miR-483-5p (miR-483) is associated with the progression of hepatocellular carcinoma (HCC). However, the significant roles of miR-483 in nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD), and HCC remain elusive. In the current study, we investigated the biological significance of miR-483 in NAFLD, AFLD, and HCC in vitro and in vivo. The downregulation of miR-483 expression in HCC patients’ tumor samples was associated with Notch 3 upregulation. Overexpression of miR-483 in a human bipotent progenitor liver cell line HepaRG and HCC cells dysregulated Notch signaling, inhibited cell proliferation/migration, induced apoptosis, and increased sensitivity towards antineoplastic agents sorafenib/regorafenib. Interestingly, the inactivation of miR-483 upregulated cell steatosis and fibrosis signaling by modulation of lipogenic and fibrosis gene expression. Mechanistically, miR-483 targets PPARα and TIMP2 gene expression, which leads to the suppression of cell steatosis and fibrosis. The downregulation of miR-483 was observed in mice liver fed with a high-fat diet (HFD) or a standard Lieber-Decarli liquid diet containing 5% alcohol, leading to increased hepatic steatosis/fibrosis. Our data suggest that miR-483 inhibits cell steatosis and fibrogenic signaling and functions as a tumor suppressor in HCC. Therefore, miR-483 may be a novel therapeutic target for NAFLD/AFLD/HCC management in patients with fatty liver diseases and HCC. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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18 pages, 835 KiB

Open AccessReview

Obstructive Sleep Apnea: A Look towards Micro-RNAs as Biomarkers of the Future

by Giorgia Moriondo, Piera Soccio, Pasquale Tondo, Giulia Scioscia, Roberto Sabato, Maria Pia Foschino Barbaro and Donato Lacedonia

Biology 2023, 12(1), 66; https://doi.org/10.3390/biology12010066 - 30 Dec 2022

Cited by 5 | Viewed by 2670

Abstract

Sleep-disordered breathing (SDB) includes a broad spectrum of diseases, of which obstructive sleep apnea syndrome (OSA) is the most clinically significant manifestation. OSA is a respiratory disorder characterized by episodes of complete or partial obstruction of the upper airways that disturb ventilation and sleep architecture. In recent years, interest in the clinical implications of OSA seems to have increased, probably due to the numerous studies that have shown the existence of an important correlation between OSA and cardiovascular, dysmetabolic, and neoplastic changes. The guidelines currently available highlight the importance of diagnosis and effective treatment for OSA, underlining the need for new biomarkers that are useful in clinical practice, feasible, and reproducible to guide medical decision making. In this review, we intend to provide an overview of the potential role of microRNAs as new indicators for OSA management. MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in RNA silencing and regulation of gene expression at the post-transcriptional level. These can bind specifically to their target genes by forming silencing complexes, thus inducing degradation or altered gene expression. A wide range of miRNAs have been extensively studied in a variety of diseases including cancer, and recently, miRNAs have been shown to have enormous potential to function as diagnostic and clinical biomarkers of disease. This review includes recent studies that establish the inevitable role of miRNAs in the pathogenesis of OSA. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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16 pages, 5516 KiB

Open AccessArticle

Evaluation of miRNA Expression in Glioblastoma Stem-Like Cells: A Comparison between Normoxia and Hypoxia Microenvironment

by Lucy Wanjiku Macharia, Wanjiru Muriithi, Dennis Kirii Nyaga, Juliana de Mattos Coelho-Aguiar, Tania Cristina Leite de Sampaio e Spohr and Vivaldo Moura-Neto

Onco 2022, 2(2), 113-128; https://doi.org/10.3390/onco2020008 - 26 May 2022

Cited by 1 | Viewed by 2935

Abstract

Purpose: Glioblastoma is an aggressive and incurable brain tumor whose progression is driven in part by glioblastoma stem cells, which are also responsible for the tumor’s low therapy efficacy. The maintenance and expansion of the stem cell population is promoted by the hypoxic microenvironment, where miRNAs play fundamental roles in their survival. Methods: GBM stem-like cells were isolated from three GBM parental cell lines. The stem-like cells were then cultured under normoxic and hypoxic microenvironments followed by investigation of the in vitro “stemness” of the cells. Results: We found miR-128a-3p, 34-5p and 181a-3p to be downregulated and miR-17-5p and miR-221-3p to be upregulated in our stem-like cells compared to the GBMs. When a comparison was made between normoxia and hypoxia, a further fold downregulation was observed for miR-34-5p, miR-128a-3p and miR-181a-3p and a further upregulation was observed for miR-221-3p and 17-5p. There was an increased expression of HIF-1/2, SOX2, OCT4, VEGF, GLUT-1, BCL2 and survivin under hypoxia. Conclusion: Our data suggest that our GBMs were able to grow as stem-like cells and as spheroids. There was a differential expression of miRNAs between the stems and the GBMs and the hypoxia microenvironment influenced further dysregulation of the miRNAs and some selected genes. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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14 pages, 1828 KiB

Open AccessArticle

Assessment of MicroRNAs Associated with Tumor Purity by Random Forest Regression

by Dong-Yeon Nam and Je-Keun Rhee

Biology 2022, 11(5), 787; https://doi.org/10.3390/biology11050787 - 21 May 2022

Cited by 3 | Viewed by 2992

Abstract

Tumor purity refers to the proportion of tumor cells in tumor tissue samples. This value plays an important role in understanding the mechanisms of the tumor microenvironment. Although various attempts have been made to predict tumor purity, attempts to predict tumor purity using miRNAs are still lacking. We predicted tumor purity using miRNA expression data for 16 TCGA tumor types using random forest regression. In addition, we identified miRNAs with high feature-importance scores and examined the extent of the change in predictive performance using informative miRNAs. The predictive performance obtained using only 10 miRNAs with high feature importance was close to the result obtained using all miRNAs. Furthermore, we also found genes targeted by miRNAs and confirmed that these genes were mainly related to immune and cancer pathways. Therefore, we found that the miRNA expression data could predict tumor purity well, and the results suggested the possibility that 10 miRNAs with high feature importance could be used as potential markers to predict tumor purity and to help improve our understanding of the tumor microenvironment. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biology biology	3.6	5.7	2012	16.4 Days	CHF 2700
Cancers cancers	4.5	8.0	2009	17.4 Days	CHF 2900
Current Oncology curroncol	2.8	3.3	1994	19.8 Days	CHF 2200
Diseases diseases	2.9	0.8	2013	21.4 Days	CHF 1800
Onco onco	-	-	2021	27.8 Days	CHF 1000

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