Role of microRNAs in B-Cell Compartment: Development, Proliferation and Hematological Diseases

Souza, Olívia Fonseca; Popi, Ana Flávia

doi:10.3390/biomedicines10082004

Cited by 12 publications

(6 citation statements)

References 158 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Through RNA sequencing and in silico analysis, KDM5B and DEPTOR emerged as candidate genes downregulated in ibrutinib-resistant cells. Both KDM5B, a histone demethylase, and DEPTOR, an mTOR phosphatase, have been implicated in tumor suppression and negative regulation of cell proliferation [27][28][29][30][31][32]. Validation experiments, including Ago2 immunoprecipitation and luciferase reporter assays, provided evidence for the direct regulation of KDM5B and DEPTOR by miR-155-5p.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Interplay of miR-155-5p Transfer in the Mechanisms Underlying Ibrutinib Resistance in DLBCL through Extracellular Vesicles

Park,

Choi,

Ryu

et al. 2024

Preprint

View full text Add to dashboard Cite

Ibrutinib, a Bruton Tyrosine Kinase (BTK) inhibitor, has exhibited efficacy in various B-cell lymphoid malignancies. However, prolonged usage may lead to resistance, impacting treatment outcomes. The oncogenic microRNA, miR-155-5p is related with poor prognosis in B-cell lymphomas, prompting our investigation into the mechanism of acquired ibrutinib resistance in B-cell lymphoma cells. To generate ibrutinib-resistant OCI-Ly1 cells (OCI-Ly1-IbtR), continuous exposure to 1µM and 2µM of ibrutinib was employed. microRNA profiling of OCI-Ly1-IbtR was conducted, and exosomes were isolated using ultracentrifugation. Comparative studies of microRNA levels in cells and exosomes, and targets of up-regulated microRNAs in OCI-Ly1-IbtR were explored. Target validation involved transfection of candidate microRNA, and co-culture experiments utilized OCI-Ly1 with exosomes from OCI-Ly1-IbtR. Elevated miR-155-5p levels were observed in OCI-Ly1-IbtR and exosomes from OCI-Ly1-IbtR, correlating with AKT and NF-κB activation. MiR-155-5p transfection induced AKT/NF-κB pathway activation in OCI-Ly1, resulting in ibrutinib resistance, enhanced colony formation and sustained BTK activity. Primary cell lines from ibrutinib-refractory B-cell lymphoma patients exhibited similar signaling protein activation. Target evaluation identified KDM5B and DEPTOR as miR-155-5p targets, confirmed by downregulation after transfection. KDM5B and DEPTOR enrichment in Ago2 during ibrutinib resistance and miR-155-5p transfection was observed. Co-culture experiments demonstrated exosome-mediated miR-155-5p transfer, inducing ibrutinib resistance and KDM5B/DEPTOR downregulation in OCI-Ly1. Our findings suggest that miR-155-5p overexpression is associated with AKT and NF-κB pathway activation in ibrutinib-resistant cells, proposing a potential role for acquired miR-155-5p upregulation in B-cell lymphoma ibrutinib resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Dynamic Interplay of miR-155-5p Transfer in the Mechanisms Underlying Ibrutinib Resistance in DLBCL through Extracellular Vesicles

Park,

Choi,

Ryu

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The differentiation of B cells from lymphoid progenitors is regulated by a series of transcription factors, including PU.1, STAT5, E2A (E12 and E47), EBF, Pax-5, IKZFI, and FOXP1 [16]. There are data on miRNA-34a and miRNA-150 involvement in FOXP1 expression regulation and B-cell development [5,6].…”

Section: Discussionmentioning

confidence: 99%

“…Other studies demonstrated that miRNA-181 and miRNA-34 are involved in the regulation of the pro-B to pre-B cell transition [5]. Souza et al noted that miRNA-150, -146a, -155, -125b, -223, and -142, as well as the let-7 family of miRNAs, control B-cell differentiation [6]. In addition, miRNA-17, -24, -146, -155, -128, and -181 regulate early stages of hematopoiesis; miRNA-16, -103, and -107 can block the differentiation of late precursors; and miRNA-221, -222, and -223 control the terminal stages of hematopoiesis differentiation [7].…”

Section: Introductionmentioning

confidence: 99%

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

Veryaskina,

Titov,

Kovynev

et al. 2023

IJMS

View full text Add to dashboard Cite

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.

show abstract

“…Therefore, these miRNAs have high clinical significance in the pathogenesis of CLL [47]. In fact, they target genes involved in cell proliferation and apoptosis such as BCL-2 (B cell lymphoma 2), CCND1, CCND3, and CDK6, and act as tumor suppressors [48]. According to in vitro research, the primary mechanisms by which miR-15a/16-1 exert their pathogenic roles in B cells are through controlling cell cycle and apoptosis, specifically by modulating the expression of genes involved in the G0/G1-S transition; for instance, by inducing the activation of G1-S-specific cyclin D2 (CCND2 and CCND3) and the antiapoptotic BCL2 gene [49,50].…”

Section: The Correlation Between Mirnas and Cll Pathogenesismentioning

confidence: 99%

MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia

Ali,

Mahla,

Reza

et al. 2024

eJHaem

View full text Add to dashboard Cite

Small noncoding ribonucleic acids called microRNAs coordinate numerous critical physiological and biological processes such as cell division, proliferation, and death. These regulatory molecules interfere with the function of many genes by binding the 3'‐UTR region of target mRNAs to inhibit their translation or even degrade them. Given that a large proportion of miRNAs behave as either tumor suppressors or oncogenes, any genetic or epigenetic aberration changeing their structure and/or function could initiate tumor formation and development. An example of such cancers is chronic lymphocytic leukemia (CLL), the most prevalent adult leukemia in Western nations, which is caused by unregulated growth and buildup of defective cells in the peripheral blood and lymphoid organs. Genetic alterations at cellular and molecular levels play an important role in the occurrence and development of CLL. In this vein, it was noted that the development of this disease is noticeably affected by changes in the expression and function of miRNAs. Many studies on miRNAs have shown that these molecules are pivotal in the prognosis of different cancers, including CLL, and their epigenetic alterations (e.g., methylation) can predict disease progression and response to treatment. Furthermore, miRNAs are involved in the development of drug resistance in CLL, and targeting these molecules can be considered a new therapeutic approach for the treatment of this disease. MiRNA screening can offer important information on the etiology and development of CLL. Considering the importance of miRNAs in gene expression regulation, their application in the diagnosis, prognosis, and treatment of CLL is reviewed in this paper.

show abstract

Role of microRNAs in B-Cell Compartment: Development, Proliferation and Hematological Diseases

Cited by 12 publications

References 158 publications

Dynamic Interplay of miR-155-5p Transfer in the Mechanisms Underlying Ibrutinib Resistance in DLBCL through Extracellular Vesicles

Dynamic Interplay of miR-155-5p Transfer in the Mechanisms Underlying Ibrutinib Resistance in DLBCL through Extracellular Vesicles

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

MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia

Contact Info

Product

Resources

About