Table 1.
MicroRNAs’ (miRNAs’) role in B-cell development, central tolerance, autoimmunity, and lymphoma.
| miRNA | Putative targets | Function | Reference |
|---|---|---|---|
| Bone marrow B-cell development | |||
| miR-17-92 cluster | Bim | Essential for fetal and adult B-cell development; promote the survival of early B-cell progenitors (pro-B→pre-B) | (14, 15) |
| miR-34a | Foxp1 | Inhibit B cell development at the pro-B to pre-B cell stage | (16) |
| miR-150 | c-Myb, Foxp1 | High levels in the lymph nodes, spleen, and thymus, premature expression block the transition from the pro-B to the pre-B stage | (17, 18) |
| miR-181 | Unknown | Essential for B-cell lineage differentiation | (12) |
| miR-23a miRNA cluster | Trib3 | Inhibit B-cell development | (20, 21) |
| miR-212/132 | Sox4 | Regulate the differentiation of prepro-B cells to pro-B cells and regulate B-cell survival | (22) |
| Peripheral B-cell development | |||
| miR-146a | Numb | Regulate marginal zone B-cell differentiation | (30) |
| miR-155 | Activation-induced cytidine deaminase | Regulate Ig isotype switching and somatic hypermutation | (31, 32) |
| PU.1 | Essential for germinal center response and high-affinity IgG1 production | (33, 34) | |
| miR-125b | BLIMP-1 and IRF-4 | Regulate B-cell differentiation in GC | (35) |
| miR-223 | LMO2 and MYBL1 | Regulate naïve to GC B cell and GC B cell to memory cell transition | (36) |
| miR-142 | B cell-activating factor-R | Maintain B cell homeostasis; mice deficiency in miR-142 lead to increased size of splenic B cell compartment and hypoimmunoglobulinemia | (37) |
| B-cell central tolerance and autoimmunity | |||
| miR-17-92 cluster | PTEN | Control B cell central tolerance at the immature B cell stage; Mice overexpressing the miR-17-92 cluster develop autoimmunity |
(15, 44) |
| miR-148a | Gadd45a, Bcl2l11, and Pten | Regulate B cell central tolerance and autoimmunity, Increased miR-148a expression lead to lethal autoimmune disease in lupus mice | (45) |
| miR-210 | Unknown | Mice deficient in miR-210 lead to production of autoantibodies; mice overexpressing miR-210 result in abnormalities in B cell subsets and function | (46) |
| B-cell lymphoma | |||
| miR-17-92 cluster | Unknown | Accelerate tumor development in a mouse B-cell lymphoma model | (48, 49) |
| miR-155 | TGFBR2, NIAM, histone deacetylase 4, SHIP1, and PIK3R1 (p85α) | Essential for cell proliferation, cell cycle, and apoptosis of diffuse large B-cell lymphoma (DLBCL) cell lines; acts as an oncogenic miR in B-cell lymphoproliferative disorders | (51–56) |
| miR-21 | Unknown | Act as oncomiR to initiate tumor formation and maintenance | (61) |
| miR-217 | Unknown | Promote the GC reaction; its overexpression promotes mature B cell lymphomagenesis | (62) |
| miR-181a | CARD11, NFKBIA, NFKB1, RELA/P65, and REL | Decrease cell proliferation and slower tumor growth rate by inhibiting NF-kB signaling activity | (63) |
| miR-34a | FoxP1, AXL | Inhibit the proliferation of various DLBCL cell lines; involve in the pathogenesis of DLBCL | (65, 66) |
| miR-146a | Early growth response-1 gene | Inhibit B-cell oncogenesis | (67, 68) |
| Cluster 15a/16-1 miRNAs | BCL2 | Tumor suppressor in B-CLL and mantle cell lymphoma | (69, 70) |
| miR-28 | MAD2L1, BAG1 | Acts as a tumor suppressor in Burkitt lymphoma | (72) |