- The Histone Acetyltransferase hMOF is Overexpressed in Non-small Cell Lung Carcinoma.
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Joon Seon Song, Sung Min Chun, Ji Young Lee, Dong Kwan Kim, Yong Hee Kim, Se Jin Jang
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Korean J Pathol. 2011;45(4):386-396.
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DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.386
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 Abstract
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- 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.
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Citations
Citations to this article as recorded by  - Stabilization of MOF (KAT8) by USP10 promotes esophageal squamous cell carcinoma proliferation and metastasis through epigenetic activation of ANXA2/Wnt signaling
Peichao Li, Lingxiao Yang, Sun Young Park, Fanrong Liu, Alex H. Li, Yilin Zhu, Huacong Sui, Fengyuan Gao, Lingbing Li, Lan Ye, Yongxin Zou, Zhongxian Tian, Yunpeng Zhao, Max Costa, Hong Sun, Xiaogang Zhao
Oncogene.2024; 43(12): 899. CrossRef - The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics
Chenise O’Garro, Loveth Igbineweka, Zonaira Ali, Mihaly Mezei, Shiraz Mujtaba
Biomolecules.2021; 11(3): 455. CrossRef - Histone Acetyltransferase MOF Orchestrates Outcomes at the Crossroad of Oncogenesis, DNA Damage Response, Proliferation, and Stem Cell Development
Mayank Singh, Albino Bacolla, Shilpi Chaudhary, Clayton R. Hunt, Shruti Pandita, Ravi Chauhan, Ashna Gupta, John A. Tainer, Tej K. Pandita
Molecular and Cellular Biology.2020;[Epub] CrossRef - The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis
Jiaming Su, Fei Wang, Yong Cai, Jingji Jin
International Journal of Molecular Sciences.2016; 17(1): 99. CrossRef - Expression of hMOF, but not HDAC4, is responsible for the global histone H4K16 acetylation in gastric carcinoma
LIN ZHU, JIAXING YANG, LINHONG ZHAO, XUE YU, LINGYAO WANG, FEI WANG, YONG CAI, JINGJI JIN
International Journal of Oncology.2015; 46(6): 2535. CrossRef - Arsenic Trioxide Reduces Global Histone H4 Acetylation at Lysine 16 through Direct Binding to Histone Acetyltransferase hMOF in Human Cells
Da Liu, Donglu Wu, Linhong Zhao, Yang Yang, Jian Ding, Liguo Dong, Lianghai Hu, Fei Wang, Xiaoming Zhao, Yong Cai, Jingji Jin, Tim Thomas
PLOS ONE.2015; 10(10): e0141014. CrossRef - The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth
Jin Zhang, Hui Liu, Hao Pan, Yuan Yang, Gang Huang, Yun Yang, Wei-Ping Zhou, Ze-Ya Pan
Biochemical and Biophysical Research Communications.2014; 452(3): 575. CrossRef - Regulation and function of histone acetyltransferase MOF
Yang Yang, Xiaofei Han, Jingyun Guan, Xiangzhi Li
Frontiers of Medicine.2014; 8(1): 79. CrossRef - The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti‐drug responses in human non‐small cell lung cancer
Zhiwei Chen, Xiangyun Ye, Naiwang Tang, Shengping Shen, Ziming Li, Xiaomin Niu, Shun Lu, Ling Xu
British Journal of Pharmacology.2014; 171(13): 3196. CrossRef - Correlation of low expression of hMOF with clinicopathological features of colorectal carcinoma, gastric cancer and renal cell carcinoma
LINGLING CAO, LIN ZHU, JIAXING YANG, JIAMING SU, JINSONG NI, YUJUN DU, DA LIU, YANFANG WANG, FEI WANG, JINGJI JIN, YONG CAI
International Journal of Oncology.2014; 44(4): 1207. CrossRef - Coactivator MYST1 Regulates Nuclear Factor-κB and Androgen Receptor Functions During Proliferation of Prostate Cancer Cells
Anbalagan Jaganathan, Pratima Chaurasia, Guang-Qian Xiao, Marc Philizaire, Xiang Lv, Shen Yao, Kerry L. Burnstein, De-Pei Liu, Alice C. Levine, Shiraz Mujtaba
Molecular Endocrinology.2014; 28(6): 872. CrossRef - A potential diagnostic marker for ovarian cancer: Involvement of the histone acetyltransferase, human males absent on the first
NING LIU, RUI ZHANG, XIAOMING ZHAO, JIAMING SU, XIAOLEI BIAN, JINSONG NI, YING YUE, YONG CAI, JINGJI JIN
Oncology Letters.2013; 6(2): 393. CrossRef - Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma
Yong Wang, Rui Zhang, Donglu Wu, Zhihua Lu, Wentao Sun, Yong Cai, Chunxi Wang, Jingji Jin
Journal of Experimental & Clinical Cancer Research.2013;[Epub] CrossRef
- Association of CXCR4 Expression with Metastasis and Survival among Patients with Non-small Cell Lung Cancer.
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Joon Seon Song, Jin Kyung Jung, Jong Chul Park, Dong Kwan Kim, Se Jin Jang
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Korean J Pathol. 2008;42(6):358-364.
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Abstract
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- BACKGROUND
Expression of CXCR4 chemokine receptor, initially described to be involved in the homing of lymphocytes in inflammatory tissue, on breast cancer cell lines is associated with the development of lung metastases.
In the present study, we evaluated CXCR4 expression in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue microarray blocks were constructed from 408 formalin-fixed, paraffin-embedded NSCLC samples and analyzed via immunohistochemical staining. RESULTS: We observed CXCR4 expression in 214 (66.3%) of the 323 tumors with cytoplasmic or nuclear staining patterns. These tumors were then divided into 109 negative, 166 weak-positive and 48 strong-positive expression groups. Strong expression of CXCR4 correlated with NSCLC recurrence (p=0.047) and distant metastasis (p=0.035). However, lymph node metastasis (p=0.683) and locoregional recurrence (p=0.856) were not associated with CXCR4 expression. Interestingly, the median overall survival times relative to CXCR4 expression were 71 months in the CXCR4-negative group, 43 months in the weakly positive CXCR4 group and 23 months in the strongly positive CXCR4 group.
Strongly positive CXCR4 staining was associated with significantly worse outcomes (p=0.005, log-rank test).
CONCLUSIONS
Expression of CXCR4 was associated with distant NSCLC metastases and shorter survival times.
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