人类Hox基因（Homeobox）在胚胎发育和癌症中发挥着重要作用。HOXC10基因是HOX家族的成员，报道称其在多种癌症中异常表达。然而，HOXC10与肝细胞癌（HCC）之间的关联尚待阐明。本研究利用组织微阵列队列数据显示，高水平的HOXC10表达预示着HCC患者的不良生存率。同时，与良性分化的细胞系HepG2和人正常肝细胞相比，Huh7细胞系中HOXC10显著上调。功能上，抑制Huh7细胞中的HOXC10能够抑制细胞增殖，增加细胞凋亡，并抑制HCC细胞的侵袭和迁移。HepG2细胞中的HOXC10过表达会增加细胞增殖，减少细胞凋亡，并增强HCC细胞的侵袭和迁移。在HepG2异种移植模型中，与对照相比，HOXC10增加了肿瘤体积和重量。机制上，METTL3通过m6A修饰HOXC10来增强其mRNA稳定性，从而增强其表达。体外和体内结果均显示过表达的HOXC10激活了PTEN/AKT/mTOR信号通路。总之，这些发现凸显了HOXC10在调控HCC进展中的重要性。HOXC10有望成为HCC治疗的未来治疗靶点。© 2023. Springer Science+Business Media, LLC.

Human Hox genes (Homeobox) play a crucial role in embryonic development and cancer. The HOXC10 gene, a member of the HOX family, has been reported abnormally expressed in several cancers. However, the association between HOXC10 and hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, tissue microarray cohort data showed that high levels of HOXC10 expression predicted a poor survival in HCC patients. Meanwhile, HOXC10 was significantly upregulated in the Huh7 cell line compared with the well differentiated cell line HepG2 and human normal liver cells. Functionally, silencing HOXC10 in Huh7 cells inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of HCC cells. HOXC10 overexpression in HepG2 cells increased cell proliferation, decreased apoptosis, and increased invasion and migration of HCC cells. In the HepG2 xenograft models, HOXC10 increased the tumor volume and weight compared with control. Mechanistically, the m6A modification of HOXC10 by METTL3 enhanced its expression by enhancing its mRNA stability. Both the in vitro and in vivo results showed that overexpressed HOXC10 activated the PTEN/AKT/mTOR pathway. In summary, the findings highlight the importance of HOXC10 in the regulation of HCC progression. HOXC10 is potentially a future therapeutic target for HCC treatment.© 2023. Springer Science+Business Media, LLC.