1. Academic Validation
  2. The aberrantly activated AURKB supports and complements the function of AURKA in CALR mutated cells through regulating the cell growth and differentiation

The aberrantly activated AURKB supports and complements the function of AURKA in CALR mutated cells through regulating the cell growth and differentiation

  • Exp Cell Res. 2025 Jan 15;444(2):114377. doi: 10.1016/j.yexcr.2024.114377.
Xueting Hu 1 Xiangru Yu 2 Liwei Zhang 2 Qigang Zhang 2 Mengchu Ji 2 Kunming Qi 1 Shujin Wang 2 Zhenyu Li 1 Kailin Xu 3 Chunling Fu 4
Affiliations

Affiliations

  • 1 Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
  • 2 Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
  • 3 Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China. Electronic address: xukl@xzhmu.edu.cn.
  • 4 Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China. Electronic address: fuchunling.bo@163.com.
Abstract

Aurora Kinase B (AURKB) was reported to assist Aurora Kinase A (AURKA) to regulate cellular mitosis. AURKA has been found activated in myeloproliferative neoplasms (MPNs) patients with CALR gene mutation, however, it's unclear whether AURKB displays a compensatory function of AURKA in regulation of CALR mutant cell growth and differentiation. Here, we found that AURKB, similar with AURKA, was aberrantly activated in CALR mutant patients, and displayed a more tolerance to the Aurora Kinase Inhibitor. Inhibition of AURKA decreased cell growth and colony formation, induced cell differentiation and Apoptosis, while, this inhibitive degree was further enhanced when AURKB was blocked by incremental inhibitor. Transcriptomic analyses revealed a more significant gene enrichment in cells with knockdown of AURKB than that of AURKA, mainly reflecting in Oxidative Phosphorylation, mitosis, proliferation and Apoptosis signaling pathway. Moreover, downregulation of AURKB enhanced cell growth arrest and Apoptosis more obviously than that of AURKA, and additionally promoted cell differentiation and metabolism-oxygen consumption rate (OCR). Otherwise, overexpression of AURKA or AURKB facilitated the cell proliferation of CALR mutant cells, and made cells more sensitive to the Aurora Kinase Inhibitor. These results suggest that activated AURKB not only supports the functions of AURKA in promoting the growth of CALR mutated cells, but also has impeded the differentiation of these cells.

Keywords

AURKB; Apoptosis; CALR gene mutation; Cell growth; Differentiation.

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