The Multifaceted Role and Utility of MicroRNAs in Indolent B-Cell Non-Hodgkin Lymphomas
Abstract
:1. Introduction
2. miRNAs in Normal B-Cell Development
2.1. miRNAs in Primary Lymphoid Tissue B-Cell Development
2.2. miRNAs in Secondary Lymphoid Tissue B-Cell Development
3. miRNAs in Follicular Lymphoma
3.1. miRNAs as Potential Regulators and Biomarkers in FL
3.2. Genetic Polymorphisms of miRNA Genes in FL
3.3. miRNAs and the Immune System
miRNAs | Sample Origin | Expression | Potential Biomarker | References |
---|---|---|---|---|
miRNAs of miR-17/92 and miR-106a-363 clusters, miR-200c-3p, miR-638, miR-518a-3p | FFPE tissues | Upregulated in DLBCL vs. FL | Differential diagnosis | [53] |
miR-17-5p | [54] | |||
miR-217-5p, miR-634, miR-26b-5p | Upregulated in FL vs. DLBCL | [53] | ||
miR-330-3p, miR-106a-5p, miR-210-3p | Upregulated in FL vs. DLBCL | [54] | ||
miR-612, miR-188-5p, miR-302c-3p, miR-433-3p, miR-584-5p | Upregulated in BCL2+/BCL6+ and BCL2−/BCL6+ FL vs. BCL2+/BCL6− FL | [51] | ||
miR-200a-3p, miR-135a-5p, miR-375-3p, miR-138-5p, miR-517 isomiRs | Downregulated in BCL2+/BCL6+ and BCL2−/BCL6+ FL vs. BCL2+/BCL6− FL | |||
miR-16-5p, miR-138-5p, miR-26a-5p, miR-29c-3p | Downregulated in t(14;18)–negative FL vs. t(14;18)–positive FL | [48] | ||
miR-193a-5p, miR-345-5p, miR-574-3p, miR-1287-5p, miR-1471 | Enriched FL cells | Upregulated in FL vs. with follicular hyperplasia | [63] | |
miR-570-3p, miR-205-5p, miR-222-3p, miR-30a-5p, miR-301b-3p, miR-141-3p | Downregulated in FL vs. with follicular hyperplasia | |||
miR-20b-5p, miR-26a-5p, miR-92b-3p, miR-487b-3p | Cancer cell lines | Upregulated in FL cell lines vs. DLBCL cell lines | [87] | |
miR-330-3p, miR-106a-5p, miR-210-3p, miR-301 isomiRs, miR-338-5p | FFPE tissues | Upregulated in FL vs. non- neoplastic lymph nodes | Diagnosis | [54] |
miR-149-5p, miR-139-5p | Downregulated in FL vs. non- neoplastic lymph nodes | |||
miR-16-5p, miR-17-5p, miR-26a-5p, miR-29a-3p, let-7d-5p, let-7g-5p, let-7i-5p | Cancer cell lines | Downregulated in FL cell lines vs. CD19+ negatively- selected B cells | [87] | |
miR-144-3p, miR-431-5p | FL biopsies and blood samples | Upregulated in relapsed FL patients | Prognosis, prediction of disease progression | [88] |
miR-376b-3p | Downregulated in non-relapsed FL patients |
4. miRNAs in Marginal Zone Lymphoma
4.1. Extranodal Marginal Zone Lymphoma or Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma
4.2. Gastric MALT Lymphoma and H. pylori
4.3. From Chronic Gastritis to MALT GL
4.4. From MALT GL to Gastric DLBCL
4.5. Non-Gastric MALT Lymphoma
4.6. Splenic Marginal Zone Lymphoma
4.7. Nodal Marginal Zone Lymphoma
Disease | miRNAs | Sample Origin | Expression | Potential Biomarker | References |
---|---|---|---|---|---|
Gastric MALT lymphoma | miR-142-3p, miR-155-5p | FFPE tissues | Upregulated in gastric MALT lymphoma vs. chronic gastritis | Differential diagnosis | [74] |
miR-203a-3p | Downregulated in gastric MALT lymphoma vs. chronic gastritis | ||||
Ocular adnexal lymphoma (OAL) | let-7g-5p, miR-16-5p, miR-29 family, miR-199a-5p, miR-222-3p | FFPE tissues | Upregulated in OAL vs. ocular DLBCL | Differential diagnosis | [118] |
Sjögren’s syndrome (SS) associated with MALT lymphoma | miR-200b-5p | Minor salivary glands and PBMCs | Downregulated in SS-associated MALT lymphoma vs. SS | Prognosis, prediction of patients’ relapse | [123,124] |
Splenic MZL (SMZL) | miR-21-5p | Fresh frozen and FFPE tissues | Upregulated in aggressive SMZL vs. indolent SMZL | Prognosis, prediction of patients’ relapse | [133] |
Nodal MZL (NMZL) | miR-223-3p, let-7f-5p | FFPE tissues | Upregulated in NMZL vs. FL | Differential diagnosis | [139] |
5. miRNAs in Rare Types of Indolent B-Cell NHLs
5.1. Waldenström’s Macroglobulinemia or Lymphoplasmacytic Lymphoma
5.2. Other Rare Types of B-Cell NHLs
Disease | miRNAs | Sample Origin | Expression | Potential Biomarker | References |
---|---|---|---|---|---|
WM | miR-363-3p, miR-206-3p, miR-494-3p, miR-155-5p, miR-184-3p, miR-542-3p | Bone marrow CD19+ B cells | Upregulated in WM vs. normal CD19+ B cells | Diagnosis | [81] |
miR-9-3p | Downregulated in WM vs. normal CD19+ B cells | ||||
miR-193b-3p, miR-126-3p, miR-181a-5p, miR-125b-5p, miR-451a | Bone marrow or peripheral blood CD19+ and CD138+ B cells | Upregulated in WM vs. CLL | Differential diagnosis | [149] | |
miR-92a-3p, miR-223-3p, miR-92b-3p, miR-363-3p | Upregulated in WM vs. MM | ||||
miR-9-3p, miR-193b-3p, miR-182-5p, miR-152-3p | Downregulated in WM vs. MM | ||||
miR-21-5p, miR-142-3p | Upregulated in WM vs. normal B-lineage cells | Diagnosis | |||
miR-182-5p, miR-152-3p, miR-373-5p, miR-575-3p | Downregulated in WM vs. normal B-lineage cells | ||||
Combination of miR-320a-3p and miR-320b-3p | Serum | Downregulated in WM vs. normal blood donors; downregulated in WM vs. MGUS and MM | Diagnosis, differential diagnosis | [151] | |
miR-151-5p, let-7a-5p | Downregulated in WM vs. normal blood donors; downregulated in WM vs. MGUS | ||||
miR-21-5p, miR-192-5p, miR-320b-3p | Exosomes | Increases with disease progression | Prediction of disease progression | [152] | |
let-7d-5p | Decreases with disease progression | ||||
HCL | miR-363-3p, miR-708-5p | Peripheral blood B cells | Downregulated in HCL vs. CLL | Differential diagnosis | [146] |
miR-221-3p, miR-222-3p, miR-22-3p, miR-24-3p, miR-27a-3p, let-7b-5p | Peripheral blood CD19+ B cells | Upregulated in HCL vs. other B-cell malignancies; upregulated in HCL vs. normal B-lineage cells | Diagnosis, differential diagnosis | [147] | |
PCFCL | miR-150-5p, miR-155-5p | FFPE tissues | Upregulated in PCFCL vs. cutaneous MZL | Differential diagnosis | [117] |
miR-129-2-3p, miR-214-3p, miR-31-5p, miR-9-5p | Upregulated in PCFCL vs. primary cutaneous DLBCL-leg type | [148] |
6. Interplay between Cytokines and miRNAs in B-Cell Malignancies
7. Limitations
8. Future Perspectives
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Disease | miRNAs | Expression in Lymphomas | Targets | Effect | References |
---|---|---|---|---|---|
Follicular lymphoma (FL) | miR-150-5p | Decreased | FOXP1 | Inhibition of B-cell survival | [59] |
miR-31-5p | E2F2, PIK3C2A | Inhibition of cell cycle, survival, and migration | [62] | ||
miR-202-3p | DICER1 | Regulation of biogenesis of miRNAs | [64] | ||
SKP2 | Regulation of cell cycle transition | ||||
miR-618 | HDAC3 | Inhibition of cell cycle | [65] | ||
CUL4A | Inhibition of DNA damage response | ||||
miR-155-5p | INPP5D | Promotion of anti-tumor immune responses | [66] | ||
miR-16-5p | CHEK1 | Promotion of B-cell apoptosis | [48] | ||
CDK6 | Inhibition of B-cell proliferation | ||||
miR-20a-5p, miR-20b-5p | Increased | CDKN1A | Promotion of cell cycle | [63] | |
miR-194-5p | SOCS2 | Promotion of B-cell proliferation and survival | |||
miR-93-5p | MICA, MICB | Inhibition of B-cell cytotoxicity | [67] | ||
Gastric MALT lymphoma | miR-34a-5p | Decreased | FOXP1 | Inhibition of B-cell survival | [22,68,69,70,71] |
miR-383-5p | ZEB2 | Inhibition of epithelial-to-mesenchymal transition (EMT) | [72] | ||
miR-203a-3p | ABL1 | Inhibition of B-cell proliferation | [73,74] | ||
miR-155-5p, miR-142-5p | Increased | TP53INP1 | Inhibition of apoptosis | [74,75,76] | |
Splenic MZL | miR-26b-5p | Decreased | NEK6 | Inhibition of mitosis-cell division | [77,78] |
Waldenström’s macroglobulinemia (WM) | miR-9-3p | Decreased | HDAC4, HDAC5 | Regulation of histone acetylation; Induction of WM cell cytotoxicity; promotion of WM cell autophagy and apoptosis | [79] |
miR-23b-3p | SP1 | Suppression of NFkB signaling; Inhibition of cell proliferation and survival | [80] | ||
miR-155-5p | Increased | - | Promotion of MAPK/ERK, PI3K/AKT, and NFkB signaling; promotion of cell proliferation, adhesion, and migration | [81,82] | |
FOXO3, BCL2L11 | Inhibition of apoptosis | [83] | |||
miR-206-3p | KAT6A | Regulation of histone acetylation | [79] |
Disease | miRNAs | Potential Target in Lymphomas | Potential Effect in B Cells | References |
---|---|---|---|---|
Gastric MALT lymphoma | miR-150-5p | MYB | Regulation of B-cell development | [14,76,100,101] |
EGR2 | Inhibition of apoptosis | |||
miR-196a-5p | CDKN1B | Promotion of cell cycle | [76,104] | |
miR-153-3p | AKT3 | Inhibition of cell proliferation | [76,105] | |
miR-7-5p | EGFR and IGF1R | Inhibition of metastasis | [76,106,107] | |
miR-16-5p | BCL2 | Promotion of apoptosis | [113,114] | |
Splenic MZL | miR-29a/b1 cluster | TCL1A | Inhibition of cell proliferation | [126,128,129,130,131] |
miR-129-5p | BCL2 | Promotion of apoptosis | ||
miR-21-5p | PTEN, FOXO3 | Promotion of cell proliferation, inhibition of apoptosis | [133,134] | |
Nodal MZL | miR-223-3p | LMO2 | Inhibition of B-cell differentiation | [42,139] |
OAL | miR-29 family | TCL1A | Inhibition of cell proliferation | [118,119] |
CDK6 | ||||
DNMT3B | Inhibition of DNA methylation | |||
MCL1 | Promotion of apoptosis | |||
miR-199a-5p | IKBKB | Promotion of apoptosis | [118,120,121] | |
WM | miR-9-3p | PDRM1 | Inhibition of B-cell differentiation | [149] |
miR-125b-5p and miR-181a-5p | PRDM1, IRF4 | |||
let-7a-5p | MYC | Inhibition of cell proliferation | [142] | |
miR-21-5p | PTEN, PDCD4 | Promotion of cell proliferation, regulation of apoptosis | [150] | |
PCFCL | miR-9-5p | PRDM1 | Inhibition of B-cell differentiation | [148] |
miR-129-2-3p | SOX4 | |||
miR-155-5p | SPI1 |
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Artemaki, P.I.; Letsos, P.A.; Zoupa, I.C.; Katsaraki, K.; Karousi, P.; Papageorgiou, S.G.; Pappa, V.; Scorilas, A.; Kontos, C.K. The Multifaceted Role and Utility of MicroRNAs in Indolent B-Cell Non-Hodgkin Lymphomas. Biomedicines 2021, 9, 333. https://doi.org/10.3390/biomedicines9040333
Artemaki PI, Letsos PA, Zoupa IC, Katsaraki K, Karousi P, Papageorgiou SG, Pappa V, Scorilas A, Kontos CK. The Multifaceted Role and Utility of MicroRNAs in Indolent B-Cell Non-Hodgkin Lymphomas. Biomedicines. 2021; 9(4):333. https://doi.org/10.3390/biomedicines9040333
Chicago/Turabian StyleArtemaki, Pinelopi I., Petros A. Letsos, Ioanna C. Zoupa, Katerina Katsaraki, Paraskevi Karousi, Sotirios G. Papageorgiou, Vasiliki Pappa, Andreas Scorilas, and Christos K. Kontos. 2021. "The Multifaceted Role and Utility of MicroRNAs in Indolent B-Cell Non-Hodgkin Lymphomas" Biomedicines 9, no. 4: 333. https://doi.org/10.3390/biomedicines9040333