Korean J Pathol.  2011 Aug;45(4):386-396.

The Histone Acetyltransferase hMOF is Overexpressed in Non-small Cell Lung Carcinoma

Affiliations
  • 1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. jangsejin@amc.seoul.kr
  • 2Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

BACKGROUND
One of the histone acetyltransferases (HATs) family of proteins, human MOF (hMOF, MYST1), is involved in histone H4 acetylation, particularly at lysine 16 (H4K16Ac), an epigenetic mark of active genes. Dysregulation of the epigenetic mark influences cellular biology and possibly leads to oncogenesis. We examined the involvement of hMOF and H4K16Ac in primary non-small cell lung cancer (NSCLC).
METHODS
Reverse transcription polymerase chain reaction using fresh-frozen lung cancer tissues and lung cancer cell lines and immunohistochemistry for hMOF and H4K16Ac via tissue microarray of 551 formalin-fixed paraffin-embedded NSCLC tissue blocks were conducted.
RESULTS
hMOF mRNA was frequently overexpressed in lung cancer tissues, compared with normal lung tissues (10/20, 50%). NSCLC tissues were positive for hMOF in 37.6% (184/489) and H4K16Ac in 24.7% (122/493) of cases. hMOF protein expression was tightly correlated with the H4K16Ac level in tumors (p<0.001). Knockdown of hMOF mRNA with siRNA led to a significant inhibition of growth in the Calu-6 cell line.
CONCLUSIONS
hMOF was frequently expressed in NSCLC and was correlated with H4K16Ac. To our knowledge, this is the first study that has focused on the expression status of HATs and hMOF in NSCLC. Our results clearly suggest a potential oncogenic role of the gene and support its utility as a potential therapeutic target.

Keyword

Carcinoma, non-small cell lung; Histones; Acetylation; Histone acetyltransferases

MeSH Terms

Acetylation
Carcinoma, Non-Small-Cell Lung
Cell Line
Cell Transformation, Neoplastic
Epigenomics
Histone Acetyltransferases
Histones
Humans
Immunohistochemistry
Lung
Lung Neoplasms
Lysine
Polymerase Chain Reaction
Proteins
Reverse Transcription
RNA, Messenger
RNA, Small Interfering
Histone Acetyltransferases
Histones
Lysine
Proteins
RNA, Messenger
RNA, Small Interfering
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