The suppressive functions of Rora in B lineage cell proliferation and BCR/ABL1-induced B-ALL pathogenesis

RORA plays an important role in regulating circadian rhythms, inflammation, metabolism and cellular development. Herein, we explore the roles of in B cell proliferation and differentiation, as well as in Ph B-ALL. By using Mx-1-Cre mice, was deleted in hematopoietic cells post Pipc induction. defici...

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Published in:International journal of biological sciences 2022-01, Vol.18 (6), p.2277-2291
Main Authors: Li, Ning, Wang, Nan, He, Wei, Feng, Yunyu, Qiu, Qiang, Qiu, Huandi, Zheng, Li, Yin, Yuexia, Wang, Bochuan, Sun, Yuanyuan, Pan, Cong, Sample, Klarke M, Huang, Juan, Su, Zhiguang, Li, Zhihui, Zhang, Haojian, Hu, Yiguo
Format: Article
Language:English
Subjects:
Ablation
Angiogenesis
Animals
Antibodies
Apoptosis
Biotechnology
Blood
Bone marrow
Bone Marrow - metabolism
Cancer
Cell Differentiation
Cell growth
Cell proliferation
Cell Proliferation - genetics
Cholesterol
Chromosomes
Circadian rhythms
Fusion Proteins, bcr-abl - genetics
Fusion Proteins, bcr-abl - metabolism
Laboratories
Leukemogenesis
Lymphocytes B
Metabolism
Mice
Pathogenesis
Peripheral blood
Research Paper
Software
Spleen
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Summary:RORA plays an important role in regulating circadian rhythms, inflammation, metabolism and cellular development. Herein, we explore the roles of in B cell proliferation and differentiation, as well as in Ph B-ALL. By using Mx-1-Cre mice, was deleted in hematopoietic cells post Pipc induction. 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 deficient B cells. Moreover, the expression of 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 in B cell development and Ph leukemogenesis.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.68939