p200CUX1-regulated BMP8B inhibits the progression of acute myeloid leukemia via the MAPK signaling pathway

作者全名：Wang, Meng; Zhong, Liang; Zhang, Hongyan; Wan, Peng; Chu, Xuan; Shao, Xin; Chen, Shuyu; Zhou, Ziwei; Yu, Lihua; Liu, Beizhong

作者地址：[Wang, Meng; Zhang, Hongyan; Wan, Peng; Chu, Xuan; Shao, Xin; Chen, Shuyu; Zhou, Ziwei; Liu, Beizhong] Chongqing Med Univ, Yongchuan Hosp, Cent Lab, Chongqing 402160, Peoples R China; [Zhong, Liang; Liu, Beizhong] Chongqing Med Univ, Minist Educ, Dept Lab Med, Key Lab Lab Med Diagnost, Chongqing 400016, Peoples R China; [Yu, Lihua] Chongqing Med Univ, Yongchuan Hosp, Clin Lab, Chongqing 402160, Peoples R China

通信作者：Liu, BZ (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Cent Lab, Chongqing 402160, Peoples R China.; Liu, BZ (通讯作者)，Chongqing Med Univ, Minist Educ, Dept Lab Med, Key Lab Lab Med Diagnost, Chongqing 400016, Peoples R China.; Yu, LH (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Clin Lab, Chongqing 402160, Peoples R China.

来源：MEDICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001236569500001

JCR分区：Q2

影响因子：2.8

年份：2024

卷号：41

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：Acute myeloid leukemia; p200CUX1; BMP8B; MAPK; Proliferation; Differentiation

摘要：The full-length p200CUX1 protein encoded by the homology frame CUT-like protein (CUX1) plays an important role in tumors as a pro-oncogene or oncogene. However, its role and mechanism in acute myeloid leukemia remain unknown. p200CUX1 regulates several pathways, including the MAPK signaling pathway. Our data showed that p200CUX1 is lowly expressed in THP1 and U937 AML cell lines. Lentiviral overexpression of p200CUX1 reduced proliferation and promoted apoptosis and G0/G1 phase blockade, correlating with MAPK pathway suppression. Additionally, p200CUX1 regulated the expression of bone morphogenetic protein 8B (BMP8B), which is overexpressed in AML. Overexpression of p200CUX1 downregulated BMP8B expression and inhibited the MAPK pathway. Furthermore, BMP8B knockdown inhibited AML cell proliferation, enhanced apoptosis and the sensitivity of ATRA-induced cell differentiation, and blocked G0/G1 transition. Our findings demonstrate the pivotal function of the p200CUX1-BMP8B-MAPK axis in maintaining the viability of AML cells. Consequently, targeting p200CUX1 could represent a viable strategy in AML therapy.

基金机构：Key Technology Innovation Special of Key Industries of the Chongqing Science and Technology Bureau

基金资助正文：No Statement Available