HOXC11 drives lung adenocarcinoma progression through transcriptional regulation of SPHK1.
Xin PengXiaoli LiuWanshan HuYanling ZhouLianlian OuyangXintong PengYao LongJingyue SunTania TaoLing ChenYing ShiKonstantin M J SparrerDesheng XiaoShuang LiuPublished in: Cell death & disease (2023)
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.
Keyphrases
- cell cycle
- transcription factor
- poor prognosis
- induced apoptosis
- human health
- signaling pathway
- risk assessment
- cell cycle arrest
- gene expression
- cell proliferation
- protein kinase
- oxidative stress
- stem cells
- tyrosine kinase
- magnetic resonance
- long non coding rna
- computed tomography
- bone marrow
- cell migration
- dna binding
- free survival
- nuclear factor