Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas

Jacob Minor, Xiaotian Wang, Fang Zhang, John Song, Antonio Jimeno, Xiao Jing Wang, Xian Lu, Neil Gross, Molly Kulesz-Martin, Daren Wang, Shi Long Lu

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Detection of DNA methylation has produced promising results as biomarkers for head and neck squamous cell carcinoma (HNSCC). However, current panels are limited by an insufficient number of sensitive and specific tumor markers. MicroRNAs (miR) play an important role in tumorigenesis, and may represent a novel panel of molecules for the development of cancer biomarkers. We investigated methylation of three miRNA promoter sites of miR-9 (miR-9-1, miR-9-2, miR-9-3) in 107 human head and neck tissue samples and controls. We found methylations of miR-9-1 and miR-9-3 were higher in oral and oropharyngeal carcinomas than that in laryngeal carcinoma, achieving a combined sensitivity of 63% and 56%, respectively, for these two tumor types, compared to 21% for the laryngeal carcinoma. Quantitative PCR of miR-9 showed reduced expression associated with methylation of miR-9 in tumor tissues. To investigate the functional consequences of miR-9 methylation, we found that miR-9 methylation is correlated with miR-9 expression level in human HNSCC cell lines. Demethylation treatment using 5-aza-deoxycytidine restored its expression in a miR-9 methylated human HNSCC cell line UM-SCC22A. Furthermore, cell proliferation and viability was significantly inhibited, while PTEN expression was elevated after transfection of miR-9 into the UM-SCC22A cell line. In summary, our results suggest that methylations of miR-9-1 and miR-9-3 are sensitive and specific biomarkers for HNSCC, particularly for oral and oropharyngeal squamous cell carcinomas. In addition, miR-9 may function as a tumor suppressor in HNSCC through inhibition of cell proliferation and elevation of tumor suppressor PTEN.

Original languageEnglish (US)
Pages (from-to)73-78
Number of pages6
JournalOral Oncology
Volume48
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

MicroRNAs
Methylation
Squamous Cell Carcinoma
Biomarkers
Tumor Biomarkers
Carcinoma
Cell Line
Neoplasms
Cell Proliferation
Deoxycytidine
DNA Methylation
Transfection

Keywords

  • Biomarkers
  • Head and neck squamous cell carcinoma
  • Methylation
  • MicroRNA

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

Cite this

Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas. / Minor, Jacob; Wang, Xiaotian; Zhang, Fang; Song, John; Jimeno, Antonio; Wang, Xiao Jing; Lu, Xian; Gross, Neil; Kulesz-Martin, Molly; Wang, Daren; Lu, Shi Long.

In: Oral Oncology, Vol. 48, No. 1, 01.2012, p. 73-78.

Research output: Contribution to journalArticle

Minor, J, Wang, X, Zhang, F, Song, J, Jimeno, A, Wang, XJ, Lu, X, Gross, N, Kulesz-Martin, M, Wang, D & Lu, SL 2012, 'Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas', Oral Oncology, vol. 48, no. 1, pp. 73-78. https://doi.org/10.1016/j.oraloncology.2011.11.006
Minor, Jacob ; Wang, Xiaotian ; Zhang, Fang ; Song, John ; Jimeno, Antonio ; Wang, Xiao Jing ; Lu, Xian ; Gross, Neil ; Kulesz-Martin, Molly ; Wang, Daren ; Lu, Shi Long. / Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas. In: Oral Oncology. 2012 ; Vol. 48, No. 1. pp. 73-78.
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AU - Wang, Xiao Jing

AU - Lu, Xian

AU - Gross, Neil

AU - Kulesz-Martin, Molly

AU - Wang, Daren

AU - Lu, Shi Long

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AB - Detection of DNA methylation has produced promising results as biomarkers for head and neck squamous cell carcinoma (HNSCC). However, current panels are limited by an insufficient number of sensitive and specific tumor markers. MicroRNAs (miR) play an important role in tumorigenesis, and may represent a novel panel of molecules for the development of cancer biomarkers. We investigated methylation of three miRNA promoter sites of miR-9 (miR-9-1, miR-9-2, miR-9-3) in 107 human head and neck tissue samples and controls. We found methylations of miR-9-1 and miR-9-3 were higher in oral and oropharyngeal carcinomas than that in laryngeal carcinoma, achieving a combined sensitivity of 63% and 56%, respectively, for these two tumor types, compared to 21% for the laryngeal carcinoma. Quantitative PCR of miR-9 showed reduced expression associated with methylation of miR-9 in tumor tissues. To investigate the functional consequences of miR-9 methylation, we found that miR-9 methylation is correlated with miR-9 expression level in human HNSCC cell lines. Demethylation treatment using 5-aza-deoxycytidine restored its expression in a miR-9 methylated human HNSCC cell line UM-SCC22A. Furthermore, cell proliferation and viability was significantly inhibited, while PTEN expression was elevated after transfection of miR-9 into the UM-SCC22A cell line. In summary, our results suggest that methylations of miR-9-1 and miR-9-3 are sensitive and specific biomarkers for HNSCC, particularly for oral and oropharyngeal squamous cell carcinomas. In addition, miR-9 may function as a tumor suppressor in HNSCC through inhibition of cell proliferation and elevation of tumor suppressor PTEN.

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