| First Author | Li N | Year | 2022 |
| Journal | Int J Biol Sci | Volume | 18 |
| Issue | 6 | Pages | 2277-2291 |
| PubMed ID | 35414788 | Mgi Jnum | J:323409 |
| Mgi Id | MGI:7261993 | Doi | 10.7150/ijbs.68939 |
| Citation | Li N, et al. (2022) The suppressive functions of Rora in B lineage cell proliferation and BCR/ABL1-induced B-ALL pathogenesis. Int J Biol Sci 18(6):2277-2291 |
| abstractText | RORA plays an important role in regulating circadian rhythms, inflammation, metabolism and cellular development. Herein, we explore the roles of Rora in B cell proliferation and differentiation, as well as in Ph(+) B-ALL. By using Rora(loxp/loxp) Mx-1-Cre mice, Rora was deleted in hematopoietic cells post Pipc induction. Rora deficiency mice were associated with an obvious accumulation of B cells in the peripheral blood, bone marrow, and spleen. On the other hand, activation of Rora with Cholesterol sulfate (CS) was associated with decreased B cell numbers. RNA-seq analysis revealed that the transcription level of Lmo1 was decreased in Rora deficient B cells. Moreover, the expression of RORA was shown to be decreased in Ph(+) B-ALL cells compared to peripheral blood derived B cells from healthy donors. The overexpression of Rora in BaF3 cells with BCR/ABL1 was also associated with impeded the cell growth and an increased apoptotic rate compared to cells transduced with BCR/ABL1 alone. The co-expression of BCR/ABL1 and Rora induced B-ALL mouse model was associated with the significant inhibition of BCR/ABL1-transformed cell growth and prolonged the survival of the diseased mice. These results suggest a novel role for Rora in B cell development and Ph(+) leukemogenesis. |
