Journal
CELLS
Volume 8, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/cells8111360
Keywords
HOXA9; NF-kappa B; apoptosis; autophagy; cutaneous squamous cell carcinoma
Categories
Funding
- National Natural Science Foundation of China [81772914]
- Guangdong Basic and Applied Basic Research Foundation, China [2016A030313738]
- Science and Technology Program of Guangzhou, China [201904010063]
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Tumor suppressor HOXA9 has been identified to promote apoptosis in cutaneous squamous cell carcinoma (cSCC). However, the mechanism of such pro-apoptotic role of HOXA9 remains obscure. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of RNA-seq data showed that NF-kappa B, apoptosis and autophagy pathways are significantly regulated after HOXA9 knockdown. HOXA9 transcriptionally regulates RELA, the p65 subunit of NF-kappa B. Loss of HOXA9 in cSCC significantly upregulates RELA expression and thus enhances NF-kappa B pathway. Interestingly, RELA transcriptionally promotes not only anti-apoptotic factor BCL-XL but also autophagic genes including ATG1, ATG3, and ATG12. Our results reveal an enhanced NF-kappa B signaling network regulated by HOXA9, which contributes to repressed apoptosis and activated autophagy in cSCC development and may represent an intervention target for cSCC therapy.
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