口腔鱗狀細胞癌是全世界常見、死亡率高的惡性腫瘤之一。造成口腔鱗狀細胞癌的主要原因包括抽菸、飲酒、嚼檳榔以及人類乳突病毒感染所引起的慢性刺激和發炎。手術切除是目前口腔鱗狀細胞癌主要的治療方式，其他治療包含放射線治療、化學治療以及免疫療法。然而，對於口腔鱗狀細胞癌晚期的病人來說，治療效果很有限。表觀基因體的調控是調控細胞生長發育和基因表現很重要的一個機制。在過去已經有很多的研究證實異常的表觀基因體調控會導致癌症的發生和惡化。表觀基因體療法是一種新治療癌症的方法用來抑制和逆轉導致癌症的表觀基因體修飾。目前表觀基因體標靶藥物對於淋巴瘤治療的效果很好，然而，這些藥物對於實體瘤卻沒有好的治療效果，原因可能為這些藥物缺乏辨識基因序列的專一性。伏立諾他（SAHA）為組蛋白去乙醯酶的抑制劑，其透過調控組蛋白的乙醯化作用來調控基因表現。吡咯咪唑聚酰胺（PIP）是可合成的寡聚物，其可以高親和力與DNA的次溝槽（minor groove）結合。將PIP和SAHA結合可以增加合成藥物對序列的識別，加強結合到特定序列。我們使用次世代定序（NGS）來分析PIP-SAHA特異性結合的基因序列，用於抑制口腔鱗狀細胞癌中的表觀基因體組蛋白乙醯化生物標誌異常調控和逆轉導致癌症的表觀遺傳修飾，藉此開發新型表觀基因體抗癌標靶藥物PIP-SAHA，用於口腔鱗狀細胞癌患者的治療。研究證實PIP-SAHA V藥物可以抑制口腔鱗狀細胞癌細胞株之增生、遷移和侵入能力。並且透過次世代定序的分析證實PIP-SAHA V藥物可以專一性的調控HNF4、RelA以及MyHC基因網絡中的組蛋白H3K9乙醯化和DNA甲基化。

Oral squamous cell carcinoma (OSCC) is one of the common malignancies worldwide with a high mortality rate. The causes of OSCC include chronic irritation and inflammation from tobacco smoking, alcohol consumption, betel nut chewing, and HPV infection. Surgical ablation is the primary treatment for OSCC, and other therapies include radiotherapy, chemotherapy, and immunotherapy. However, for advanced OSCC, its efficacy is limited. Epigenetic mechanisms are required to maintain normal growth, development and gene expression in different organs. Several studies demonstrated the epigenetic dysregulations in tumorigenesis and cancer development. Epigenetic therapy is a new method of cancer treatment and attempt to inhibit and reverse the epigenetic dysregulations that cause cancer. The epigenetic targeting drugs are effective for lymphoma therapy, however they are not efficacious for solid tumor therapy might because of lacking specificity gene targeting. Vorinostat (SAHA) is a histone deacetylase (HDACs) inhibitor that functions by altering the histone acetylation to modulate gene expression. Hairpin pyrrole-imidazole polyamides (PIP) are synthetic oligomers with programmable sequence recognition that bind the minor groove of DNA with high affinity. Conjugate PIP and SAHA may increase sequence recognition and reverse the epigenetic modifications that cause cancer. We used next generation sequencing (NGS) to analysis SAHA specific recognition gene sequences for targeting the epigenetic deregulation biomarker in OSCC. We confirmed PIP-SAHA V inhibit the proliferation, migration and invasion of oral squamous cell carcinoma cell lines. The PIP-SAHA V specifically regulated HNF4, RelA and MyHC network related gene H3K9 acetylation and DNA methylation.

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