In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 1948-1948
Abstract:
High-risk human papillomaviruses (e.g., HPV-16 and HPV-18) are closely associated with the development of human head and neck squamous cell carcinomas (HNSCC), including malignant lesions in the oral cavity. However, less is known about the possible role and the underlying mechanisms of HPV in enhancing cancer progression and promoting the virulence of cancer, including oral squamous cell carcinoma (OSCC). Cancer stem cells (CSCs) play crucial role in cancer progression, metastasis and recurrence, and are epigenetically regulated by microRNAs (miRNAs). Recent studies demonstrated that miRNA expression is affected by HPV status in HNSCC, suggesting a possible role of HPV in epigenetic regulation of CSCs. In this study, we investigated the role of high-risk HPV on malignant and CSC phenotypes as well as epigenetic regulation in OSCC. Incorporation of HPV-16 whole genome into HPV-negative OSCCs resulted in enhancement of malignant phenotypes (e.g., increased anchorage independent growth, proliferation in organotypic epithelial raft culture, and tumorigenicity in nude mice) and CSC phenotypes (e.g., increased CSC-related markers, self-renewal, and migration/invasion). High-throughput miRNA expression analysis revealed that miRNA-181 family members were significantly underexpressed in the HPV16-harboring OSCCs. HPV-16 downregulated the promoter activity of miR-181a. Furthermore, restoration of miR-181 in the presence of HPV-16 suppressed CSC-like phenotype. Taken together our data indicate that high-risk HPV enhances stemness phenotypes in OSCC by epigenetic regulation of miR-181 expression. Citation Format: Sung Hee Hee Lee, Nicole Rigas, Chang-Ryul Lee, Jiho Han, Reuben Kim, Mo Kang, No-Hee Park, Ki-Hyuk Shin. Human papillomavirus enhances oral cancer stem cell phenotype by regulating microRNA-181. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1948. doi:10.1158/1538-7445.AM2014-1948
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-1948
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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