AIFM2通过激活SIRT1/PGC-1α信号通路促进线粒体生物发生，从而增强肝细胞癌的转移。
AIFM2 promotes hepatocellular carcinoma metastasis by enhancing mitochondrial biogenesis through activation of SIRT1/PGC-1α signaling.
发表日期：2023 Sep 21
作者：
Sanxing Guo, Fengying Li, Yixuan Liang, Yufei Zheng, Yingyi Mo, Deyao Zhao, Zhixiong Jiang, Mengmeng Cui, Lixia Qi, Jiaxing Chen, Lixin Wan, Guoyong Chen, Sidong Wei, Qi Yang, Junqi Liu
来源：
Oncogenesis
摘要：
AIFM2是一个关键的NADH氧化酶，参与调节细胞质NAD+。然而，AIFM2在人类癌症进展中的作用仍然尚未被广泛探索。在本研究中，我们阐明了AIFM2在肝细胞癌（HCC）中的临床意义、生物学功能和分子机制。我们发现AIFM2在HCC中显著上调，这可能是由DNA甲基化降低和miR-150-5p下调导致的。AIFM2的高表达与HCC患者的差生存显著相关。AIFM2的沉默显著削弱了HCC的转移，而AIFM2的过表达则增强了HCC的转移，无论是体外还是体内。从机制上看，通过激活SIRT1/PGC-1α信号通路增加线粒体生物合成和氧化磷酸化有助于AIFM2在HCC中促进转移。总之，AIFM2的上调通过激活SIRT1/PGC-1α信号通路在促进HCC转移中起着关键作用，这强烈暗示AIFM2可能是治疗HCC的一个靶点。 © 2023. Springer Nature America, Inc.
AIFM2 is a crucial NADH oxidase involved in the regulation of cytosolic NAD+. However, the role of AIFM2 in the progression of human cancers remains largely unexplored. Here, we elucidated the clinical implications, biological functions, and molecular mechanisms of AIFM2 in hepatocellular carcinoma (HCC). We found that AIFM2 is significantly upregulated in HCC, which is most probably caused by DNA hypomethylation and downregulation of miR-150-5p. High expression of AIFM2 is markedly associated with poor survival in patients with HCC. Knockdown of AIFM2 significantly impaired, while forced expression of AIFM2 enhanced the metastasis of HCC both in vitro and in vivo. Mechanistically, increased mitochondrial biogenesis and oxidative phosphorylation by activation of SIRT1/PGC-1α signaling contributed to the promotion of metastasis by AIFM2 in HCC. In conclusion, AIFM2 upregulation plays a crucial role in the promotion of HCC metastasis by activating SIRT1/PGC-1α signaling, which strongly suggests that AIFM2 could be targeted for the treatment of HCC.© 2023. Springer Nature America, Inc.