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.

AIFM2 是一种重要的 NADH 氧化酶，参与细胞质 NAD ⁺的调节。然而，AIFM2 在人类癌症进展中的作用在很大程度上仍未被探索。在这里，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 中显着上调，这很可能是由 DNA 低甲基化和 miR-150-5p 下调引起的。AIFM2 的高表达与 HCC 患者的较差生存率显着相关。AIFM2 的敲除显着损害，而 AIFM2 的强制表达则增强 HCC 的体外和体内转移。从机制上讲，通过激活 SIRT1/PGC-1α 信号传导增加线粒体生物发生和氧化磷酸化有助于 AIFM2 在 HCC 中促进转移。总之，AIFM2上调通过激活SIRT1/PGC-1α信号在促进HCC转移中发挥着至关重要的作用，这有力地表明AIFM2可以作为HCC治疗的靶点。