| First Author | Mitsumura T | Year | 2018 |
| Journal | Blood Adv | Volume | 2 |
| Issue | 23 | Pages | 3483-3491 |
| PubMed ID | 30530754 | Mgi Jnum | J:294550 |
| Mgi Id | MGI:6454132 | Doi | 10.1182/bloodadvances.2018017954 |
| Citation | Mitsumura T, et al. (2018) Ablation of miR-146b in mice causes hematopoietic malignancy. Blood Adv 2(23):3483-3491 |
| abstractText | Excessive and constitutive activation of nuclear factor-kappaB (NF-kappaB) leads to abnormal cell proliferation and differentiation, leading to the development of malignant tumors, including lymphoma. MicroRNA 146a (miR-146a) and miR-146b, both of which carry an identical seed sequence, have been shown to contribute to inflammatory diseases and tumors by suppressing the expression of key molecules required for NF-kappaB activation. However, the functional and physiological differences between miR-146a and miR-146b in disease onset have not been fully elucidated. In this study, we generated miR-146b-knockout (KO) and miR-146a-KO mice by genome editing and found that both strains developed hematopoietic malignancies such as B-cell lymphoma and acute myeloid leukemia during aging. However, the B-cell lymphomas observed in miR-146a- and miR-146b-KO mice were histologically different in their morphology, and the malignancy rate is lower in miR-146b mice than miR-146a mice. Upon mitogenic stimulation, the expression of miR-146a and miR-146b was increased, but miR-146b expression was lower than that of miR-146a. Using a previously developed screening system for microRNA targets, we observed that miR-146a and miR-146b could target the same mRNAs, including TRAF6, and inhibit subsequent NF-kappaB activity. Consistent with these findings, both miR-146a- and miR-146b-KO B cells showed a high proliferative capacity. Taken together, sustained NF-kappaB activation in miR-146b KO mice could lead to the development of hematopoietic malignancy with aging. |
