Department of Pediatrics, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China.
Fujian Children's Hospital, Fuzhou, China.
Cell Biol Toxicol. 2023 Dec;39(6):2631-2645. doi: 10.1007/s10565-023-09792-y. Epub 2023 Jan 30.
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.
新兴的报告表明，长非编码 RNA（lncRNA）在癌症的发病机制和转移中发挥作用。然而，LncRNA CEBPA-AS1 在急性髓系白血病（AML）中的生物学功能和潜在机制在很大程度上仍未被揭示。通过荧光原位杂交（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的 CEBPA-AS1 水平。应用体内和体外功能测试来确定 CEBPA-AS1 在 AML 发展中的致癌作用。过表达的 CEBPA-AS1 与 AML 患者的不良生存相关。此外，通过生物信息学预测了 CEBPA-AS1、锌指蛋白 X 连锁（ZFX）和 miR-24-3p 之间的关系，并通过 RNA 免疫沉淀（RIP）和荧光素酶报告基因测定进行了验证。我们的研究结果揭示了转录因子 ZFX 特别与 CEBPA-AS1 的启动子相互作用并激活 CEBPA-AS1 的转录。CEBPA-AS1 的下调抑制了 AML 细胞的增殖和侵袭，同时促进了体外和体内的细胞凋亡，以及异种移植肿瘤的生长。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 RNA（ceRNA）来减弱 miR-24-3p 对其下游靶标 CTBP2 的抑制作用。总之，这项研究强调了 CEBPA-AS1 在 AML 中的致癌作用，并说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 中的致癌过程提供了重要的见解。
