International Journal of Molecular Sciences

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13 pages, 1383 KiB

Open AccessArticle

MicroRNA Expression Profile in Bone Marrow and Lymph Nodes in B-Cell Lymphomas

by Yuliya A. Veryaskina, Sergei E. Titov, Igor B. Kovynev, Tatiana I. Pospelova, Sofya S. Fyodorova, Yana Yu. Shebunyaeva, Dina V. Sumenkova and Igor F. Zhimulev

Int. J. Mol. Sci. 2023, 24(20), 15082; https://doi.org/10.3390/ijms242015082 - 11 Oct 2023

Viewed by 967

Abstract

Hodgkin’s lymphomas (HL) and the majority of non-Hodgkin’s lymphomas (NHL) derive from different stages of B-cell differentiation. MicroRNA (miRNA) expression profiles change during lymphopoiesis. Thus, miRNA expression analysis can be used as a reliable diagnostic tool to differentiate tumors. In addition, the identification [...] Read more.

Hodgkin’s lymphomas (HL) and the majority of non-Hodgkin’s lymphomas (NHL) derive from different stages of B-cell differentiation. MicroRNA (miRNA) expression profiles change during lymphopoiesis. Thus, miRNA expression analysis can be used as a reliable diagnostic tool to differentiate tumors. In addition, the identification of miRNA’s role in lymphopoiesis impairment is an important fundamental task. The aim of this study was to analyze unique miRNA expression profiles in different types of B-cell lymphomas. We analyzed the expression levels of miRNA-18a, -20a, -96, -182, -183, -26b, -34a, -148b, -9, -150, -451a, -23b, -141, and -128 in lymph nodes (LNs) in the following cancer samples: HL (n = 41), diffuse large B-cell lymphoma (DLBCL) (n = 51), mantle cell lymphoma (MCL) (n = 15), follicular lymphoma (FL) (n = 12), and lymphadenopathy (LA) (n = 37), as well as bone marrow (BM) samples: HL (n = 11), DLBCL (n = 42), MCL (n = 14), FL (n = 16), and non-cancerous blood diseases (NCBD) (n = 43). The real-time RT-PCR method was used for analysis. An increase in BM expression levels of miRNA-26b, -150, and -141 in MCL (p < 0.01) and a decrease in BM levels of the miR-183-96-182 cluster and miRNA-451a in DLBCL (p < 0.01) were observed in comparison to NCBD. We also obtained data on increased LN levels of the miR-183-96-182 cluster in MCL (p < 0.01) and miRNA-18a, miRNA-96, and miRNA-9 in FL (p < 0.01), as well as decreased LN expression of miRNA-150 in DLBCL (p < 0.01), and miRNA-182, miRNA-150, and miRNA-128 in HL (p < 0.01). We showed that miRNA expression profile differs between BM and LNs depending on the type of B-cell lymphoma. This can be due to the effect of the tumor microenvironment. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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11 pages, 1495 KiB

Open AccessArticle

Circulatory miRNAs as Correlates of Elevated Intra-Pancreatic Fat Deposition in a Mixed Ethnic Female Cohort: The TOFI_Asia Study

by Farha Ramzan, Ivana R. Sequeira-Bisson, Louise W. Lu, Cameron J. Mitchell, Randall F. D’Souza, Mark H. Vickers, Sally D. Poppitt and David Cameron-Smith

Int. J. Mol. Sci. 2023, 24(18), 14393; https://doi.org/10.3390/ijms241814393 - 21 Sep 2023

Viewed by 1468

Abstract

Ectopic lipid accumulation, including intra-pancreatic fat deposition (IPFD), exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified as correlating with clinical measures of pancreatitis, pancreatic cancer and type 1 diabetes. The aim of the current study was [...] Read more.

Ectopic lipid accumulation, including intra-pancreatic fat deposition (IPFD), exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified as correlating with clinical measures of pancreatitis, pancreatic cancer and type 1 diabetes. The aim of the current study was therefore to examine the association between circulating abundances of candidate miRNAs, IPFD and liver fat deposition as quantified using magnetic resonance imaging (MRI) and spectroscopy (MRS). Asian Chinese (n = 34; BMI = 26.7 ± 4.2 kg/m²) and European Caucasian (n = 34; BMI = 28.0 ± 4.5 kg/m²) females from the TOFI_Asia cohort underwent MRI and MRS analysis of pancreas (MR-%IPFD) and liver fat (MR-%liver fat), respectively, to quantify ectopic lipid deposition. Plasma miRNA abundances of a subset of circulatory miRNAs associated with IPFD and liver fat deposition were quantified by qRT-PCR. miR-21-3p and miR-320a-5p correlated with MR-%IPFD, plasma insulin and HOMA2-IR, but not MR-%liver fat. MR-%IPFD remained associated with decreasing miR-21-3p abundance following multivariate regression analysis. miR-21-3p and miR-320a were demonstrated to be negatively correlated with MR-%IPFD, independent of ethnicity. For miR-21-3p, this relationship persists with the inclusion of MR-%liver fat in the model, suggesting the potential for a wider application as a specific circulatory correlate of IPFD. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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16 pages, 2329 KiB

Open AccessArticle

MicroRNAs Present in Malignant Pleural Fluid Increase the Migration of Normal Mesothelial Cells In Vitro and May Help Discriminate between Benign and Malignant Effusions

by Marta Marqués, Mariona Pont, Iván Hidalgo, Maria Alba Sorolla, Eva Parisi, Antonieta Salud, Anabel Sorolla and José M. Porcel

Int. J. Mol. Sci. 2023, 24(18), 14022; https://doi.org/10.3390/ijms241814022 - 13 Sep 2023

Viewed by 1913

Abstract

The sensitivity of pleural fluid (PF) analyses for the diagnosis of malignant pleural effusions (MPEs) is low to moderate. Knowledge about the pathobiology and molecular characteristics of this condition is limited. In this study, the crosstalk between stromal cells and tumor cells was [...] Read more.

The sensitivity of pleural fluid (PF) analyses for the diagnosis of malignant pleural effusions (MPEs) is low to moderate. Knowledge about the pathobiology and molecular characteristics of this condition is limited. In this study, the crosstalk between stromal cells and tumor cells was investigated in vitro in order to reveal factors that are present in PF which can mediate MPE formation and aid in discriminating between benign and malignant etiologies. Eighteen PF samples, in different proportions, were exposed in vitro to mesothelial MeT-5A cells to determine the biological effects on these cells. Treatment of normal mesothelial MeT-5A cells with malignant PF increased cell viability, proliferation, and migration, and activated different survival-related signaling pathways. We identified differentially expressed miRNAs in PF samples that could be responsible for these changes. Consistently, bioinformatics analysis revealed an enrichment of the discovered miRNAs in migration-related processes. Notably, the abundance of three miRNAs (miR-141-3p, miR-203a-3, and miR-200c-3p) correctly classified MPEs with false-negative cytological examination results, indicating the potential of these molecules for improving diagnosis. Malignant PF produces phenotypic and functional changes in normal mesothelial cells. These changes are partly mediated by certain miRNAs, which, in turn, could serve to differentiate malignant from benign effusions. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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10 pages, 2413 KiB

Open AccessArticle

MicroRNA-22 Is a Key Regulator of Lipid and Metabolic Homeostasis

by Riccardo Panella, Andreas Petri, Bhavna N. Desai, Sharmila Fagoonee, Cody A. Cotton, Piercen K. Nguyen, Eric M. Lundin, Alexandre Wagshal, Da-Zhi Wang, Anders M. Näär, Ioannis S. Vlachos, Eleftheria Maratos-Flier, Fiorella Altruda, Sakari Kauppinen and Pier Paolo Pandolfi

Int. J. Mol. Sci. 2023, 24(16), 12870; https://doi.org/10.3390/ijms241612870 - 17 Aug 2023

Cited by 6 | Viewed by 1844

Abstract

Obesity is a growing public health problem associated with increased risk of type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease (NAFLD) and cancer. Here, we identify microRNA-22 (miR-22) as an essential rheostat involved in the control of lipid and energy homeostasis as [...] Read more.

Obesity is a growing public health problem associated with increased risk of type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease (NAFLD) and cancer. Here, we identify microRNA-22 (miR-22) as an essential rheostat involved in the control of lipid and energy homeostasis as well as the onset and maintenance of obesity. We demonstrate through knockout and transgenic mouse models that miR-22 loss-of-function protects against obesity and hepatic steatosis, while its overexpression promotes both phenotypes even when mice are fed a regular chow diet. Mechanistically, we show that miR-22 controls multiple pathways related to lipid biogenesis and differentiation. Importantly, genetic ablation of miR-22 favors metabolic rewiring towards higher energy expenditure and browning of white adipose tissue, suggesting that modulation of miR-22 could represent a viable therapeutic strategy for treatment of obesity and other metabolic disorders. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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15 pages, 1991 KiB

Open AccessArticle

Salivary miRNA Profiles in COVID-19 Patients with Different Disease Severities

by Irma Saulle, Micaela Garziano, Gioia Cappelletti, Fiona Limanaqi, Sergio Strizzi, Claudia Vanetti, Sergio Lo Caputo, Mariacristina Poliseno, Teresa Antonia Santantonio, Mario Clerici and Mara Biasin

Int. J. Mol. Sci. 2023, 24(13), 10992; https://doi.org/10.3390/ijms241310992 - 1 Jul 2023

Cited by 1 | Viewed by 1175

Abstract

The oral mucosa is the first site of SARS-CoV-2 entry and replication, and it plays a central role in the early defense against infection. Thus, the SARS-CoV-2 viral load, miRNAs, cytokines, and neutralizing activity (NA) were assessed in saliva and plasma from mild [...] Read more.

The oral mucosa is the first site of SARS-CoV-2 entry and replication, and it plays a central role in the early defense against infection. Thus, the SARS-CoV-2 viral load, miRNAs, cytokines, and neutralizing activity (NA) were assessed in saliva and plasma from mild (MD) and severe (SD) COVID-19 patients. Here we showed that of the 84 miRNAs analyzed, 8 were differently expressed in the plasma and saliva of SD patients. In particular: (1) miRNAs let-7a-5p, let-7b-5p, and let-7c-5p were significantly downregulated; and (2) miR-23a and b and miR-29c, as well as three immunomodulatory miRNAs (miR-34a-5p, miR-181d-5p, and miR-146) were significantly upregulated. The production of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-9, and TNFα) and chemokines (CCL2 and RANTES) increased in both the saliva and plasma of SD and MD patients. Notably, disease severity correlated with NA and immune activation. Monitoring these parameters could help predict disease outcomes and identify new markers of disease progression. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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9 pages, 523 KiB

Open AccessCommunication

miR-18a and miR-106a Signatures in Plasma Small EVs Are Promising Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma

by Xiaohui Xu, Kritisha Bhandari, Chao Xu, Katherine Morris and Wei-Qun Ding

Int. J. Mol. Sci. 2023, 24(8), 7215; https://doi.org/10.3390/ijms24087215 - 13 Apr 2023

Cited by 7 | Viewed by 1273

Abstract

Pancreatic cancer is the third leading cause of cancer-related death in the United States. Pancreatic ductal adenocarcinoma (PDAC) is the major form of pancreatic cancer with the worst outcomes. Early detection is key to improving the overall survival rate of PDAC patients. Recent [...] Read more.

Pancreatic cancer is the third leading cause of cancer-related death in the United States. Pancreatic ductal adenocarcinoma (PDAC) is the major form of pancreatic cancer with the worst outcomes. Early detection is key to improving the overall survival rate of PDAC patients. Recent studies have demonstrated that microRNA (miRNA) signatures in plasma small extracellular vesicles (EVs) are potential biomarkers for the early detection of PDAC. However, published results are inconsistent due to the heterogeneity of plasma small EVs and the methods used for small EV isolation. We have recently refined the process of plasma small EV isolation using double filtration and ultracentrifugation. In the present study, we applied this protocol and analyzed plasma small EV miRNA signatures by small RNA sequencing and quantitative RT-PCR in a pilot cohort, consisting of patients with early-stage PDAC, and age- and gender-matched healthy subjects (n = 20). We found, via small RNA sequencing, that there are several miRNAs enriched in plasma small EVs of PDAC patients, and the levels of miR-18a and miR-106a were confirmed by quantitative RT-PCR to be significantly elevated in patients with early-stage PDAC compared with age- and gender-matched healthy subjects. Furthermore, using an immunoaffinity-based plasma small EV isolation approach, we confirmed that the levels of miR-18a and miR-106a in plasma small EVs were significantly higher in PDAC patients versus the healthy subjects. We thus conclude that the levels of miR-18a and miR-106a in plasma small EVs are promising biomarkers for the early detection of PDAC. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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Review

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22 pages, 406 KiB

Open AccessReview

Tiny Guides, Big Impact: Focus on the Opportunities and Challenges of miR-Based Treatments for ARDS

by Chirag M. Vaswani, Julia Simone, Jacqueline L. Pavelick, Xiao Wu, Greaton W. Tan, Amin M. Ektesabi, Sahil Gupta, James N. Tsoporis and Claudia C. dos Santos

Int. J. Mol. Sci. 2024, 25(5), 2812; https://doi.org/10.3390/ijms25052812 - 28 Feb 2024

Cited by 1 | Viewed by 1056

Abstract

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung inflammation and increased membrane permeability, which represents the leading cause of mortality in ICUs. Mechanical ventilation strategies are at the forefront of supportive approaches for ARDS. Recently, an increasing understanding of RNA biology, function, [...] Read more.

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung inflammation and increased membrane permeability, which represents the leading cause of mortality in ICUs. Mechanical ventilation strategies are at the forefront of supportive approaches for ARDS. Recently, an increasing understanding of RNA biology, function, and regulation, as well as the success of RNA vaccines, has spurred enthusiasm for the emergence of novel RNA-based therapeutics. The most common types of RNA seen in development are silencing (si)RNAs, antisense oligonucleotide therapy (ASO), and messenger (m)RNAs that collectively account for 80% of the RNA therapeutics pipeline. These three RNA platforms are the most mature, with approved products and demonstrated commercial success. Most recently, miRNAs have emerged as pivotal regulators of gene expression. Their dysregulation in various clinical conditions offers insights into ARDS pathogenesis and offers the innovative possibility of using microRNAs as targeted therapy. This review synthesizes the current state of the literature to contextualize the therapeutic potential of miRNA modulation. It considers the potential for miR-based therapeutics as a nuanced approach that incorporates the complexity of ARDS pathophysiology and the multifaceted nature of miRNA interactions. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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24 pages, 1141 KiB

Open AccessReview

Circulating microRNA Panels for Detection of Liver Cancers and Liver-Metastasizing Primary Cancers

by Branislava Ranković and Nina Hauptman

Int. J. Mol. Sci. 2023, 24(20), 15451; https://doi.org/10.3390/ijms242015451 - 22 Oct 2023

Viewed by 1147

Abstract

Malignant liver tumors, including primary malignant liver tumors and liver metastases, are among the most frequent malignancies worldwide. The disease carries a poor prognosis and poor overall survival, particularly in cases involving liver metastases. Consequently, the early detection and precise differentiation of malignant [...] Read more.

Malignant liver tumors, including primary malignant liver tumors and liver metastases, are among the most frequent malignancies worldwide. The disease carries a poor prognosis and poor overall survival, particularly in cases involving liver metastases. Consequently, the early detection and precise differentiation of malignant liver tumors are of paramount importance for making informed decisions regarding patient treatment. Significant research efforts are currently directed towards the development of diagnostic tools for different types of cancer using minimally invasive techniques. A prominent area of focus within this research is the evaluation of circulating microRNA, for which dysregulated expression is well documented in different cancers. Combining microRNAs in panels using serum or plasma samples derived from blood holds great promise for better sensitivity and specificity for detection of certain types of cancer. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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Other

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24 pages, 8654 KiB

Open AccessHypothesis

Strategy for Pre-Clinical Development of Active Targeting MicroRNA Oligonucleotide Therapeutics for Unmet Medical Needs

by Marc Thibonnier and Sujoy Ghosh

Int. J. Mol. Sci. 2023, 24(8), 7126; https://doi.org/10.3390/ijms24087126 - 12 Apr 2023

Cited by 1 | Viewed by 2054

Abstract

We present here an innovative modular and outsourced model of drug research and development for microRNA oligonucleotide therapeutics (miRNA ONTs). This model is being implemented by a biotechnology company, namely AptamiR Therapeutics, in collaboration with Centers of Excellence in Academic Institutions. Our aim [...] Read more.

We present here an innovative modular and outsourced model of drug research and development for microRNA oligonucleotide therapeutics (miRNA ONTs). This model is being implemented by a biotechnology company, namely AptamiR Therapeutics, in collaboration with Centers of Excellence in Academic Institutions. Our aim is to develop safe, effective and convenient active targeting miRNA ONT agents for the metabolic pandemic of obesity and metabolic-associated fatty liver disease (MAFLD), as well as deadly ovarian cancer. Full article

(This article belongs to the Special Issue The Role of microRNA in Human Diseases 2.0)

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