An Emerging Issue in Oncogenic Virology: the Role of Beta Human Papillomavirus Types in the Development of Cutaneous Squamous Cell Carcinoma

ABSTRACT Evidence suggests that beta human papillomaviruses (HPVs), together with ultraviolet radiation, contribute to the development of cutaneous squamous cell carcinoma. Beta HPVs appear to be not the main drivers of carcinogenesis but rather facilitators of the accumulation of ultraviolet-induced DNA mutations. Beta HPVs are promoters of skin carcinogenesis, although they are dispensable for the maintenance of the malignant phenotype. Therefore, beta HPV represents a target for skin cancer prevention, especially in high-risk populations.

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The Role of Human Papillomaviruses and Polyomaviruses in BRAF-Inhibitor Induced Cutaneous Squamous Cell Carcinoma and Benign Squamoproliferative Lesions

Frontiers in Microbiology ◽

10.3389/fmicb.2018.01806 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 7

Author(s):

Karin J. Purdie ◽

Charlotte M. Proby ◽

Hasan Rizvi ◽

Heather Griffin ◽

John Doorbar ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Braf Inhibitor ◽

Cutaneous Squamous Cell Carcinoma ◽

Human Papillomaviruses

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A Natural History of Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Microbiomes

mBio ◽

10.1128/mbio.01432-18 ◽

2018 ◽

Vol 9 (5) ◽

Cited By ~ 4

Author(s):

David L. A. Wood ◽

Nancy Lachner ◽

Jean-Marie Tan ◽

Stephanie Tang ◽

Nicola Angel ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Actinic Keratosis ◽

Cutaneous Squamous Cell Carcinoma ◽

Human Papillomaviruses ◽

Content Type ◽

Photodamaged Skin

ABSTRACTCutaneous squamous cell carcinoma (SCC) is the second-most-common cancer in Australia. The majority of SCCs progress from premalignant actinic keratosis (AK) lesions that form on chronically sun-exposed skin. The role of skin microbiota in this progression is not well understood; therefore, we performed a longitudinal microbiome analysis of AKs and SCCs using a cohort of 13 SCC-prone immunocompetent men. The majority of variability in microbial profiles was attributable to subject, followed by time and lesion type.PropionibacteriumandMalasseziaorganisms were relatively more abundant in nonlesional photodamaged skin than in AKs and SCCs.Staphylococcuswas most commonly associated with lesional skin, in particular, sequences most closely related toStaphylococcus aureus. Of 11S. aureus-like operational taxonomic units (OTUs), six were significantly associated with SCC lesions across seven subjects, suggesting their specific involvement with AK-to-SCC progression. If a causative link exists between certainS. aureus-like OTUs and SCC etiology, therapeutic approaches specifically targeting these bacteria could be used to reduce SCC.IMPORTANCEActinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) are two of the most common dermatologic conditions in Western countries and cause substantial morbidity worldwide. The role of human papillomaviruses under these conditions has been well studied yet remains inconclusive. One PCR-based study has investigated bacteria in the etiology of these conditions; however, no study has investigated the microbiomes of AK and SCC more broadly. We longitudinally profiled the microbiomes of 112 AK lesions, profiled cross sections of 32 spontaneously arising SCC lesions, and compared these to matching nonlesional photodamaged control skin sites. We identified commonly occurring strains ofPropionibacteriumandMalasseziaat higher relative abundances on nonlesional skin than in AK and SCC lesions, and strains ofStaphylococcus aureuswere relatively more abundant in lesional than nonlesional skin. These findings may aid in the prevention of SCC.

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Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

Integrative Cancer Therapies ◽

10.1177/15347354211031646 ◽

2021 ◽

Vol 20 ◽

pp. 153473542110316

Author(s):

Liang Wang ◽

Lei Xu ◽

Yu Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Dna Methyltransferase ◽

Cutaneous Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Dependent Manner ◽

Concentration Gradients ◽

A431 Cells

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.

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