STAT3調控EZH2表現進而影響口腔癌的轉移

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STAT3调控EZH2表现进而影响口腔癌的转移

STAT3-mediated EZH2 expression modulates migration and invasion of oral cancer

林孟瑾 , 硕士　　导师：陈令仪　　

英文

口腔癌；转移； EZH2 ； oral cancer ； STAT3 ； ADAMTS1 ； MMP3 ； metastasis

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摘要 │ 参考文献 (134) │ 国际计量

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The cancer mortality rate of oral cancer has risen from the sixth to the fifth place in the past decade in Taiwan. More than 90% of oral cancers are oral squamous cell carcinomas (OSCC). Currently, patients with malignant oral cancer are treated with surgery to remove a large proportion of tumor, followed by radiation therapy or chemotherapy to destroy any remaining cancer cells. However, many patients developed recurrence after treatment, especially for those who suffered from lymphatic metastasis and distant metastasis. Thus, preventing metastasis is a way to reduce recurrence. In this thesis, we investigated the possible mechanism that promotes metastasis of OSCC. To this end, we used an OSCC cell line, OC3, which was derived from a betel nut-chewing oral cancer patient, and a more invasive line, IV2, to study the mechanism of OSCC invasion. We found that the expression of EZH2, a histone methyltransferase responsible for tri-methylation of histone H3 at lysine 27 (H3K27me3), was lower in the more invasive IV2 cells compared to that in OC3 cells. Consistent with this finding, knocking down EZH2 in OC3 cells enhanced migration and invasion. Several target genes of EZH2 have been identified, including ADAMTS1, MMP3, ROS1, CXCL1 and GLI1. To determine what leads to reduced EZH2 in IV2 cells, chromatin immunoprecipitation (ChIP) analysis suggests the involvement of STAT3 in the transcriptional expression of EZH2. In fact, STAT3 level was reduced in IV2 cells compared to OC3 cells. Knocking down STAT3 or inhibiting STAT3 decreased EZH2 expression and increased EZH2 target genes, ADAMTS1, ROS1, CXCL1 and GLI1, to regulate cell migration, invasion and proliferation. We also determined the feedback regulation between STAT3 and IL8 signaling, an upstream of STAT3. Taken together, these findings implicate that EZH2 may serve as a tumor suppressor by inhibiting metastasis-related genes in OSCC cells.

参考文献 ( 134 ) 〈TOP〉

1. Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D., and Bray, F. (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer 136, E359-386
连结：
2. Warnakulasuriya, S. (2009) Global epidemiology of oral and oropharyngeal cancer. Oral oncology 45, 309-316
连结：
3. Dionne, K. R., Warnakulasuriya, S., Zain, R. B., and Cheong, S. C. (2015) Potentially malignant disorders of the oral cavity: current practice and future directions in the clinic and laboratory. International journal of cancer 136, 503-515
连结：
4. Markopoulos, A. K. (2012) Current aspects on oral squamous cell carcinoma. Open Dent J 6, 126-130
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5. Petti, S. (2009) Lifestyle risk factors for oral cancer. Oral oncology 45, 340-350
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引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。