ZFX介导的CEBPA-AS1上调通过miR-24-3p/CTBP2轴促进急性髓性白血病的进展。
ZFX-mediated upregulation of CEBPA-AS1 contributes to acute myeloid leukemia progression through miR-24-3p/CTBP2 axis.
发表日期:2023 Jan 30
作者:
Chengyi Wang, Chao-Min Song, Shan Liu, Lu-Min Chen, Shu-Fang Xue, Si-Han Huang, Han Lin, Guang-Hua Liu
来源:
CELL BIOLOGY AND TOXICOLOGY
摘要:
新出现的报告表明,长非编码RNA(lncRNA)在癌症的发病和转移中发挥作用。然而,LncRNA CEBPA-AS1在急性髓样白血病(AML)中的生物功能和潜在机制仍然不明确。利用荧光原位杂交(FISH)和逆转录定量聚合酶链反应(RT-qPCR)检测AML临床组织和细胞系中CEBPA-AS1的水平。应用体内和体外功能测试以鉴定CEBPA-AS1在AML发展中的增癌作用。过表达的CEBPA-AS1与AML患者的不良生存率有关。此外,生物信息学预测并通过RNA免疫共沉淀(RIP)和荧光素酶报告基因实验验证了CEBPA-AS1、锌指蛋白X-连锁(ZFX)和miR-24-3p之间的关系。我们的发现揭示了转录因子ZFX特别相互作用于CEBPA-AS1启动子并激活CEBPA-AS1转录。CEBPA-AS1的下调抑制了AML细胞的增殖和侵袭,同时促进细胞凋亡,在体内和体外的异种移植瘤生长中有变化。然而,CEBPA-AS1的过表达观察到相反的效果。此外,CEBPA-AS1作为miR-24-3p的竞争性内源性RNA(ceRNA),以减弱miR-24-3p对其下游靶点CTBP2的抑制作用。总的来说,这项研究强调了CEBPA-AS1在AML中的增癌作用,并阐明了它与上游转录因子ZFX和下游调节轴miR-24-3p/CTBP2的联系,为AML中的癌症过程提供了重要见解。©2023年。作者(们)在Springer Nature B.V.拥有独家许可。
Emerging reports demonstrated that long non-coding RNAs (lncRNAs) play a role in the pathogenesis and metastasis of cancers. However, the biological functions and underlying mechanisms of LncRNA CEBPA-AS1 in acute myeloid leukemia (AML) remain largely elusive. The level of CEBPA-AS1 was examined in AML clinical tissues and cell lines via fluorescence in situ hybridization (FISH) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In vivo and in vitro functional tests were applied to identify the pro-oncogenic role of CEBPA-AS1 in AML development. The overexpressed CEBPA-AS1 was linked to poor survival in AML patients. Moreover, the relationships among CEBPA-AS1, Zinc Finger Protein X-Linked (ZFX), and miR-24-3p were predicted by bioinformatics and validated by RNA immunoprecipitation (RIP) and luciferase reporter assays. Our findings unveiled that transcription factor ZFX particularly interacted with the promoter of CEBPA-AS1 and activated CEBPA-AS1 transcription. Downregulation of CEBPA-AS1 inhibited the proliferation and invasion while promoted apoptosis of AML cells in in vitro, as well as in vivo, xenograft tumor growth was modified. However, overexpression of CEBPA-AS1 observed the opposite effects. Furthermore, CEBPA-AS1 acted as a competitive endogenous RNA (ceRNA) of miR-24-3p to attenuate the repressive effects of miR-24-3p on its downstream target CTBP2. Taken together, this study emphasized the pro-oncogenic role of CEBPA-AS1 in AML and illustrated its connections with the upstream transcription factor ZFX and the downstream regulative axis miR-24-3p/CTBP2, providing important insights to the cancerogenic process in AML.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.