scholarly journals Dysregulated Protein Translation Control in Hidradenitis Suppurativa: Implication for Lesion-associated Squamous Cell Carcinoma Development

2021 ◽  
Author(s):  
Lin Jin ◽  
Mahendra P Kashyap ◽  
Yunjia Chen ◽  
Yuanyuan Guo ◽  
Jasim Khan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Squamous Cell ◽  
Hidradenitis Suppurativa ◽  
Protein Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Pathway Enrichment Analysis ◽  
Translation Control

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.

scholarly journals N6-Methyladenosine Methyltransferase METTL14-Mediated Autophagy in Malignant Development of Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fang Wang ◽  
Yue Zhu ◽  
Hongshi Cai ◽  
Jianfeng Liang ◽  
Wenjin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Translation Efficiency ◽  
Rna Methylation

N6-methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotes and is related to stability, localization, or translation efficiency in tumorigenesis. Autophagy plays an important role in the occurrence and development of tumours. However, the relationship between m6A and autophagy remains unclear. In this study, we used a rapamycin-induced autophagy model of oral squamous cell carcinoma (OSCC) cells, and observed increased m6A RNA methylation. When autophagy was activated, the methyltransferase-like 14 (METTL14) expression was upregulated and influenced the proliferation, migration, and invasiveness of OSCC cells. Through meRIP-seq and RNA-seq analysis, we found that METTL14 directly combined with eukaryotic translation initiation factor gamma 1 (eIF4G1) mRNA and decreased its RNA stability. According to the dual-luciferase reporter and mutagenesis assay, the mutated site 1 of exon 11 of eIF4G1 is the key target of METTL14. Knockdown of the main m6A binding protein YTHDF2 may rescue the shortened half-life of eIF4G1 mRNA induced by METTL14 overexpression. Furthermore, an in vivo tumour xenograft model confirmed that a high METTL14 expression can effectively reduce OSCC growth. Additionally, using clinical samples, we found that patients with advanced or moderately/poorly differentiated tumours exhibited lower METTL14 levels. Taken together, our results revealed that METTL14 mediated eIF4G1 expression via m6A modification and regulated autophagy levels and biological functions in OSCC. Our findings not only expand our understanding of the correlation between autophagy and RNA methylation in tumorigenesis but also present an opportunity to develop new therapeutic options.

scholarly journals Overexpression of eIF3a in Squamous Cell Carcinoma of the Oral Cavity and Its Putative Relation to Chemotherapy Response

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Rita Spilka ◽  
Klaus Laimer ◽  
Felix Bachmann ◽  
Gilbert Spizzo ◽  
Alexander Vogetseder ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Tumor Marker ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Study Cohort ◽  
Platinum Based Chemotherapy

The eukaryotic translation initiation factor eIF3a is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. It is known to play an important role in general translation initiation as well as in the specific translational regulation of various gene products, among which many influence tumour development, progression, and the therapeutically important pathways of DNA damage repair. Therefore, beyond its role in protein synthesis, eIF3a is emerging as regulator in tumour pathogenesis and therapy response and, therefore, a potential tumor marker. By means of a tissue microarray (TMA) for histopathological and statistical assessment, we here show eIF3a expression in 103 cases of squamous cell carcinoma of the oral cavity (OSCC), representing tissues from 103 independent patients. A subset of the study cohort was treated with platinum based therapy. Our results show that the 170 kDa protein is upregulated in OSCC and correlates with good overall survival. Overexpressing tumors respond better to platinum-based chemotherapy, suggesting eIF3a as a putative predictive as well as prognostic tumor marker in OSCC.

scholarly journals Cutaneous squamous cell carcinoma arising in hidradenitis suppurativa: A case report

2019 ◽  
Vol 7 ◽  
pp. 2050313X1984735 ◽  
Author(s):  
Catherine F Roy ◽  
Simon F Roy ◽  
Feras M Ghazawi ◽  
Erica Patocskai ◽  
Annie Bélisle ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hidradenitis Suppurativa ◽  
Rare Complication ◽  
Excisional Biopsy ◽  
Necrosis Factor Alpha ◽  
Spindle Cells ◽  
Poorly Differentiated ◽  
Well Differentiated

We present a case of a 64-year-old man who presented with a rapidly growing tumor in the left buttock and intergluteal cleft area, which was affected by hidradenitis suppurativa. The patient was on tumor necrosis factor-alpha inhibitors for hidradenitis suppurativa for 2 years prior to the development of the mass. Initial biopsy of the mass showed a well-differentiated squamous cell carcinoma with spindle cells and positive epithelial immunomarkers. Subsequent excisional biopsy of the tumor showed an infiltrating poorly differentiated squamous cell carcinoma composed of islands of atypical sarcomatoid spindle cells. Squamous cell carcinoma arising in hidradenitis suppurativa is a rare complication which may occur secondary to chronic inflammation and epidermal hyperproliferation in hidradenitis suppurativa–affected areas.

scholarly journals Cutaneous Squamous Cell Carcinoma in Patients with Hidradenitis Suppurativa

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1153
Author(s):  
Elysia Racanelli ◽  
Abdulhadi Jfri ◽  
Amnah Gefri ◽  
Elizabeth O’Brien ◽  
Ivan Litvinov ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hidradenitis Suppurativa ◽  
Case Reports ◽  
Rare Complication ◽  
Cox Proportional Hazards ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Statistical Hypothesis ◽  
Statistical Hypothesis Testing

Background: Cutaneous squamous cell carcinoma (cSCC) is a rare complication of hidradenitis suppurativa (HS). Objectives: To conduct a systematic review and an individual patient data (IPD) meta-analysis to describe the clinical characteristics of HS patients developing cSCC and determine predictors of poor outcome. Methods: Medline/PubMed, Embase, and Web of Science were searched for studies reporting cSCC arising in patients with HS from inception to December 2019. A routine descriptive analysis, statistical hypothesis testing, and Kaplan–Meier survival curves/Cox proportional hazards regression models were performed. Results: A total of 34 case reports and series including 138 patients were included in the study. The majority of patients were males (81.6%), White (83.3%), and smokers (n = 22/27 reported) with a mean age of 53.5 years. Most patients had gluteal (87.8%), Hurley stage 3 HS (88.6%). The mean time from the diagnosis of HS to the development of cSCC was 24.7 years. Human papillomavirus was identified in 12/38 patients tested. Almost 50% of individuals had nodal metastasis and 31.3% had distant metastases. Half of the patients succumbed to their disease. Conclusions: cSCC is a rare but life-threatening complication seen in HS patients, mainly occurring in White males who are smokers with severe, long-standing gluteal HS. Regular clinical examination and biopsy of any suspicious lesions in high-risk patients should be considered. The use of HPV vaccination as a preventive and possibly curative method needs to be explored.

Squamous cell carcinoma arising within hidradenitis suppurativa: a literature review

2021 ◽  
Author(s):  
Muskaan Sachdeva ◽  
Asfandyar Mufti ◽  
Hiba Zaaroura ◽  
Abrahim Abduelmula ◽  
Rafael Paolo Lansang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Literature Review ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hidradenitis Suppurativa
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