HOXA9 Transcriptionally Promotes Apoptosis and Represses Autophagy by Targeting NF-κB in Cutaneous Squamous Cell Carcinoma

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2019 Nov 6

PMID 31683603

Citations 20

Authors

Shuo Han

Xue Li

Xiaoting Liang

Liang Zhou

Affiliations

Soon will be listed here.

Abstract

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-κB, apoptosis and autophagy pathways are significantly regulated after HOXA9 knockdown. HOXA9 transcriptionally regulates RELA, the p65 subunit of NF-κB. Loss of HOXA9 in cSCC significantly upregulates RELA expression and thus enhances NF-κB 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-κB 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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