Lung adenocarcinoma (LUAD) is a fatal threat to human health, while the mechanism remains unclear, and the therapy brings limited therapeutic effects. Transcription factor Homeobox C11 (HOXC11) was previously proved to be related to hind limbs and metanephric development during the embryonic phase, and its role in tumors has been gradually recognized. Our study found that HOXC11 overexpressed in LUAD and was associated with worse overall survival. Moreover, its expression in lung cancer was regulated by IκB kinase α (IKKα), a pivotal kinase in NF-κB signaling, which was related to the ubiquitination of HOXC11. We further proved that HOXC11 could enhance the ability of proliferation, migration, invasion, colony formation, and the progression of the cell cycle in LUAD cells. Meanwhile, it also accelerated the formation of subcutaneous and lung metastases tumors. In contrast, loss of HOXC11 in LUAD cells significantly inhibited these malignant phenotypes. At the same time, HOXC11 regulated the expression of sphingosine kinase 1 (SPHK1) by directly binding to its promoter region. Therefore, we conclude that HOXC11 impacts the development of LUAD and facilitates lung cancer progression by promoting the expression of SPHK1.

肺腺癌（LUAD）是人类健康的致命威胁，但其机制尚不明确，治疗效果有限。转录因子Homeobox C11（HOXC11）先前被证明与胚胎期后肢和后肾发育有关，其在肿瘤中的作用逐渐被认可。我们的研究发现 HOXC11 在 LUAD 中过表达并且与较差的总生存期相关。此外，其在肺癌中的表达受 IκB 激酶 α (IKKα) 调节，IκB 激酶 α (IKKα) 是 NF-κB 信号通路中的关键激酶，与 HOXC11 的泛素化有关。我们进一步证明HOXC11可以增强LUAD细胞的增殖、迁移、侵袭、集落形成和细胞周期进程的能力。同时，它还加速了皮下和肺转移肿瘤的形成。相反，LUAD 细胞中 HOXC11 的缺失显着抑制了这些恶性表型。同时，HOXC11 通过直接结合其启动子区域来调节鞘氨醇激酶 1 (SPHK1) 的表达。因此，我们得出结论，HOXC11 通过促进 SPHK1 的表达影响 LUAD 的发展并促进肺癌进展。