PT  - JOURNAL ARTICLE
AU  - Lin Jin
AU  - Mahendra P. Kashyap
AU  - Yunjia Chen
AU  - Yuanyuan Guo
AU  - Jasim Khan
AU  - Jari Q. Chen
AU  - Madison B Lee
AU  - Zhiping Weng
AU  - Allen Oak
AU  - Rajesh Sinha
AU  - M. Shahid Mukhtar
AU  - Jessy S. Deshane
AU  - Chander Raman
AU  - Craig A. Elmets
AU  - Mohammad Athar
TI  - Dysregulated Protein Translation Control in Hidradenitis Suppurativa: Implication for Lesion-associated Squamous Cell Carcinoma Development
AID  - 10.1101/2021.10.14.464300
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.14.464300
4099  - http://biorxiv.org/content/early/2021/10/15/2021.10.14.464300.short
4100  - http://biorxiv.org/content/early/2021/10/15/2021.10.14.464300.full
AB  - Hidradenitis Suppurativa (HS) is a proinflammatory painful skin disorder. This chronic disease is often associated with aggressive squamous cell carcinoma (SCC). The molecular pathogenesis of this disease progression remains undefined. The translation initiation factor eIF4E/4G/4A1 complex is overexpressed in a variety of human malignancies. In this study, we found that the expression of eIF4E/4G/4A1 as well as phosphorylated eIF4E were upregulated in HS skin. In the global transcription profiles derived from two public database, we were able to enrich 734 eIF4F-related genes. GSEA pathway enrichment analysis further demonstrated that RAS/MEK/ERK oncogene signaling pathway associated with inflammation signaling were significantly activated in HS lesion. The increase expression of eIF4 protein components was associated with enhanced eIF4E translation targets Cyclin D1 and c-Myc. Confocal fluorescence microscopy analysis further revealed that Cyclin D1 and c-Myc specifically co-localized in nuclei of certain cells in HS epithelium. We also found that many of the PCNA positive hyperproliferative cells were also positive for c-Myc expression. These data demonstrate that 5’-cap□dependent translation is a potential pathway underlying the SCC pathogenesis in chronic HS lesions. Furthermore, being a druggable target, inhibition of eIF4F may block lesion-associated lethal SCCs in HS patients.Competing Interest StatementThe authors have declared no competing interest.