Histone acetyltransferase hMOF promotes S phase entry and tumorigenesis in lung cancer

Zhao, Lei; Wang, Da-Liang; Liu, Yan; Su, Chunxia; Sun, Fang-Lin

doi:10.1016/j.cellsig.2013.04.006

Cited by 50 publications

(61 citation statements)

References 51 publications

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“…Accordingly, MOF overexpression correlates with increased cellular proliferation, oncogenic transformation and tumour growth (Gupta et al, 2008). Abnormal gene expression of hMOF is involved in certain primary cancers, including breast cancer (Kapoor-Vazirani et al, 2011), renal cell carcinoma , ovarian cancer , medulloblastoma (Pfister et al, 2008), as well as lung cancers (Song et al, 2011;Zhao et al, 2013). Song et al (2011) found that hMOF mRNA was frequently overexpressed in lung cancer tissues and that hMOF knockdown led to a significant inhibition of growth in the Calu-6 cell line.…”

Section: Discussionmentioning

confidence: 99%

The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti‐drug responses in human non‐small cell lung cancer

Chen

Tang

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEThe histone acetyltransferase MOF is a member of the MYST family. In mammals, MOF plays critical roles by acetylating histone H4 at K16 and non-histone substrates such as p53. Here we have investigated the role of MOF in human lung cancer and possible new substrates of hMOF. EXPERIMENTAL APPROACHSamples of human non-small cell lung cancer (NSCLC) were used to correlate MOF with clinicopathological parameters and NF-E2-related factor 2 (Nrf2) downstream genes. 293T-cells were used to study interactions between MOF and Nrf2, and acetylation of Nrf2 by MOF. Mouse embryonic fibroblast and A549 cells were utilized to assess involvement of MOF in antioxidative and anti-drug responses. A549 cells were used to analysis the role of MOF in anti-drug response in vitro and in vivo. KEY RESULTShMOF was overexpressed in human NSCLC tissues and was associated with large tumour size, advanced disease stage and metastasis, and with poor prognosis. hMOF levels were positively correlated with Nrf2-downstream genes. MOF/hMOF physically interacted with and acetylated Nrf2 at Lys 588 . MOF-mediated acetylation increased nuclear retention of Nrf2 and transcription of its downstream genes. Importantly, MOF/hMOF was essential for anti-oxidative and anti-drug responses in vitro and regulated tumour growth and drug resistance in vivo in an Nrf2-dependent manner. CONCLUSION AND IMPLICATIONShMOF was overexpressed in human NSCLC and was a predictor of poor survival. hMOF-mediated Nrf2 acetylation and nuclear retention are essential for anti-oxidative and anti-drug responses. hMOF may provide a therapeutic target for the treatment of NSCLC. AbbreviationsARE, antioxidant response element; CDDP, cis-diamminedichloroplatinum; GCLM, glutamate-cysteine ligase modifier subunit; HO-1, haem oxygenase 1; Keap1, Kelch-like ECH-associated protein 1; MEF, mouse embryonic fibroblast; MOF, males absent on the first; MSL, male-specific lethal; Nrf2, NF-E2-related factor 2; NQO1, NAD(P)H quinone oxidoreductase 1; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil

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Section: Discussionmentioning

confidence: 99%

The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti‐drug responses in human non‐small cell lung cancer

Chen

Tang

et al. 2014

British J Pharmacology

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“…Frequent downregulation of hMOF in primary breast carcinomas, renal cell carcinoma and medulloblastomas was found, and the reduction of hMOF protein expression tightly correlated with acetylation of H4K16 in those tumors (20,21). In contrast, the expression of hMOF in non-small cell lung carcinoma tissues was frequently elevated (22,23).…”

Section: Discussionmentioning

confidence: 91%

“…Frequent downregulation of hMOF expression was found in breast cancer, medulloblastoma and RCC (20,21). On the contrary, hMOF was overexpressed in non-small cell lung carcinoma tissues (22,23). In all occasions, hMOF protein expression tightly correlated with acetylation of histone H4K16.…”

Section: Introductionmentioning

confidence: 83%

Correlation of low expression of hMOF with clinicopathological features of colorectal carcinoma, gastric cancer and renal cell carcinoma

Cao

Zhu

Yang

et al. 2014

International Journal of Oncology

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Abstract. Human MOF (males absent on the first), as a histone acetyltransferase, is responsible for histone H4K16 acetylation in human cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here, we first report the involvement of hMOF expression in clinically diagnosed primary colorectal carcinoma (CRC) and gastric cancer. Simultaneously, the correlation of hMOF expression and clinicopathological features in CRC, gastric cancer and renal cell carcinoma (RCC) was analyzed. The hMOF mRNA expression was assessed in 44 CRC, 16 gastric cancer and 47 RCC human tissue samples by quantitative PCR (qPCR). Statistical analysis of qPCR data revealed a significant reduction (>2-fold decrease) of hMOF gene expression in CRC, 57% (25/44), 94% (15/16) in gastric cancer and 74% (35/47) in RCC tissues of the patients. In patients with CRC, lymph node metastasis and tumor stage were associated with hMOF expression patterns. However, no significant association between hMOF expression and tumor types emerged (p>0.05). Interestingly, in patients with gastric cancer, although no statistically significant difference was found between adjacent (<2 cm away from the cancer tissue) and normal tissues (>5 cm away from the cancer tissue), >2-fold reduction of hMOF expression in adjacent tissues had already appeared in 35% of patients. In addition, low expression of hMOF was strongly correlated with tumor differentiation (p<0.05) and survival of patients with gastric cancer (p<0.001). While in patients with RCC, downregulation of hMOF was connected to ccRCC and tissues with T1 tumor status. Our results suggest that downregulation of hMOF may be common in cancer tissues, and may represent a novel biomarker for tumor diagnosis.

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“…Previous studies indicated that hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma (19), human renal cell (20), and colorectal carcinoma, and gastric cancer (23). However, the expression of hMOF was reportedly much higher in NSCLC compared to corresponding normal tissues, and hMOF promoted the proliferation, metastasis and adhesion of NSCLC cell lines (21). Therefore hMOF may play different roles in various malignant tumors.…”

Section: Discussionmentioning

confidence: 98%

“…In a study on human renal cell carcinoma, Wang et al found that the expression of hMOF in cancer tissues was significantly lower than that in adjacent kidney tissues (20). However, hMOF was more frequently found to be highly expressed in non-small cell lung cancer (NSCLC) than corresponding normal tissues, and hMOF promoted the proliferation, metastasis and adhesion of NSCLC cell lines (21).…”

Section: Introductionmentioning

confidence: 99%

Expression of hMOF in different ovarian tissues and its effects on ovarian cancer prognosis

Cai

Liu

et al. 2014

Oncology Reports

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Abstract. Human MOF (hMOF) is a major acetylase of human H4K16 involved in the regulation of physiological and pathological processes. We investigated the expression of hMOF in different ovarian tissues and its correlation with ovarian cancer prognosis. Reverse transcription PCR and western blot analysis were used to detect hMOF mRNA and protein expression, respectively, in different ovarian tissues. Immunohistochemistry was also performed to detect hMOF expression in different ovarian tissues, including ovarian epithelial cancer, borderline tumor, benign tumor and normal ovarian tissues. In addition, the relationships between hMOF expression and clinicopathological ovarian cancer data were analyzed. The Cox proportional-hazards regression model was used to analyze the factors associated with ovarian cancer prognosis. To analyze the effects of hMOF expression on ovarian cancer prognosis, a survival curve was plotted from the follow-up data of 77 patients with ovarian cancer. Compared with normal ovarian tissues, hMOF mRNA and protein expression was significantly decreased in ovarian epithelial cancer tissues. The proportions of high hMOF expression in normal and benign ovarian epithelial tumor tissues, were much higher than those in ovarian epithelial cancer tissues. Furthermore, hMOF protein expression was closely associated with the ovarian cancer stage. The expression of hMOF protein was determined as an independent risk factor influencing ovarian cancer prognosis. Patients with high hMOF levels showed improved survival than those with low hMOF levels. hMOF mRNA and protein expression decreased in ovarian epithelial cancer, thus the hMOF protein potentially serves as a new clinical marker of ovarian cancer prognosis.

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Histone acetyltransferase hMOF promotes S phase entry and tumorigenesis in lung cancer

Cited by 50 publications

References 51 publications

The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti‐drug responses in human non‐small cell lung cancer

The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti‐drug responses in human non‐small cell lung cancer

Correlation of low expression of hMOF with clinicopathological features of colorectal carcinoma, gastric cancer and renal cell carcinoma

Expression of hMOF in different ovarian tissues and its effects on ovarian cancer prognosis

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