乙醯轉移酶MOZ隸屬於組蛋白乙醯轉移酶(Histone acetyltransferase, HATs)中的MYST家族，可藉由將組蛋白乙醯化來改變電荷組成而使DNA構型改變，達到調控下游基因轉錄轉譯的能力；近年來少數研究指出，MYST家族可能是調控DNA損傷修復關鍵。
順鉑(Cisplatin)是目前癌症化療的重要用藥，其可以透過對癌細胞內的DNA產生嚴重損傷而達到殺死癌細胞的效用，現今廣泛運用於肺癌、卵巢癌、乳癌等，然癌細胞產生抗藥現象至今仍是癌症醫療的一大關卡。研究指出，癌細胞抗藥性產生與自身的DNA損傷修復能力增強可能有極大關連。順鉑所引發的DNA損傷主要是由范可尼貧血修復路徑(Fanconi anemia, FA)以及後複製修復路徑(Post-replication repair, PRR)配合同源重組(Homologous recombination, HR)的方式來做修復。本篇研究發現將具有順鉑抗藥性的鼻咽癌細胞株(Hone6, H6)之MOZ基因表現量抑制後，除了FA以及PRR路徑上相關蛋白的mRNA以及蛋白表現量降低以及姊妹染色分體互換率(Sister chromatid exchange, SCE)有明顯下降的現象外，細胞也會有較高機率產生stalled fork之現象，並對於順鉑藥物更具有敏感性；最後在染色質免疫沉澱(Chromatin immunoprecipitation, ChIP)實驗中發現，MOZ會與FA以及PRR之關鍵蛋白BRCA1以及FANCD2啟動子有交互作用，也就是轉錄起始點上游的位置。總結以上實驗結果推測，MOZ本身藉由結合到DNA修復路徑相關基因的啟動子上，產生chromatin remodeling而利於轉錄，進而提升修復路徑相關基因表現，達到增強癌細胞抗順鉑藥物的能力，為治療具順鉑抗藥性的癌症研究上提供一個方向。

MOZ belongs to the MYST family of histone acetyltransferases and it can acetylate histone H3 and non-histone proteins such as p53. Therefore, it plays an important role in regulating chromatin structure, transcription, DNA replication, and DNA repair. Several lines of evidence have shown that homologous recombination (HR) can contribute to the cisplatin-resistant phenotype of cancer. In this study, we hypothesize that MOZ can enhance the expression of genes in the homologous recombination repair pathway, therefore conferring cancer cells the cisplatin-resistant phenotype. Here, we found that depletion of MOZ can sensitize the cisplatin-resistant nasopharyngeal carcinoma cells, HONE6 cells, to cisplatin. In addition, the MOZ-deficient HONE6 cells show reduced expression level of several genes involved in the HR, Fanconi anemia (FA), and post-replication repair (PRR) pathways, decreased frequency of the sister chromatid exchange (SCE), and increased frequency of stalled forks in response to cisplatin. Furthermore, MOZ can bind to the promoter of BRCA1 and FANCD2 by the chromatin immunoprecipitation experiments. Our results indicate that MOZ could activate the HR repair pathway, resulting in cisplatin resistant phenotype. Targeting MOZ could be a potential therapeutic strategy to treat cisplatin resistant cancer.

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