p110CUX1 promotes acute myeloid leukemia progression via regulating pyridoxal phosphatase expression and activating PI3K/AKT/mTOR signaling pathway

Author:

Zhang Hongyan1,Zhong Liang2,Wang Meng1,Wan Peng1,Chu Xuan1,Chen Shuyu1,Zhou Ziwei1,Shao Xin1,Liu Beizhong12

Affiliation:

1. Central Laboratory of Yongchuan Hospital Chongqing Medical University Chongqing China

2. Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine Chongqing Medical University Chongqing China

Abstract

AbstractAs an evolutionarily conserved transcription factor, Cut‐like homeobox 1 (CUX1) plays crucial roles in embryonic and nervous system development, cell differentiation, and DNA damage repair. One of its major isoforms, p110CUX1, exhibits stable DNA binding capabilities and contributes to the regulation of cell cycle progression, proliferation, migration, and invasion. While p110CUX1 has been implicated in the progression of various malignant tumors, its involvement in acute myeloid leukemia (AML) remains uncertain. This study aims to elucidate the role of p110CUX1 in AML. Our findings reveal heightened expression levels of both p110CUX1 and pyridoxal phosphatase (PDXP) in AML cell lines. Overexpression of p110CUX1 promotes AML cell proliferation while inhibiting apoptosis and differentiation, whereas knockdown of PDXP yields contrasting effects. Mechanistically, p110CUX1 appears to facilitate AML development by upregulating PDXP expression and activating the PI3K/AKT/mTOR signaling pathway. Animal experimental corroborate the pro‐AML effect of p110CUX1. These results provide experimental evidence supporting the involvement of the p110CUX1‐PDXP‐PI3K/AKT/mTOR axis in AML progression. Hence, targeting p110CUX1 may hold promise as a therapeutic strategy for AML.

Publisher

Wiley

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