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The influence of histone acetyltransferase MYST4 on carcinomas
MYST4,hepatocellular carcinoma,migration,histone acetyltransferase (HAT),
|Publication Year :||2013|
|Abstract:||組蛋白乙醯化酶(HATs)在控制細胞生長和發育過程中扮演了關鍵的角色。然而一個已知的組蛋白乙醯化酶 MYST4與人類腫瘤發展的關係卻不明確。在我們先前的研究中，我們發現 MYST4在卵巢高惡性度漿液癌中有過量表現，且其過量表現與病患的較差預後有顯著相關。因此，我們想知道MYST4是否在其它腫瘤也有相同的現象。在這篇研究中，我們提供證據顯示MYST4與腫瘤的生長和進展有關。我們首先利用免疫染色發現MYST 4在肝癌及乳癌有高度表現，而且MYST4表現量跟肝癌患者存活率有顯著相關，這是第一個證據顯示MYST4可能參與肝細胞癌之進展。為了進一步了解 MYST4 基因在腫瘤細胞扮演的功能，我們利用定量逆轉錄聚合酶反應挑選出MYST4表現量高的腫瘤細胞株，包含A2780 卵巢癌細胞、SKBR3乳癌細胞及Huh7 肝癌細胞來進行敲減。細胞生長試驗及流式細胞儀細試驗的結果顯示MYST4有助於癌細胞之生長並且調控細胞週期。此外，在細胞移行試驗中，我們發現敲減MYST4 基因的細胞株其移行的能力大幅下降。這項發現指出MYST4促使腫瘤移行。我們進行微陣列試驗並發現多項基因之表現量在MYST4敲減下有負調節的現象，其中有幾個基因被證實參與腫瘤細胞之轉移。總歸而言，我們的研究顯示MYST4促使腫瘤細胞生長及移行。MYST4的高度表現會使腫瘤具有更侵犯的能力。|
Histone acetyltransferases (HATs) play a critical role in the process of controlling cell growth and development. However, little is known about the relationship between MYST4, a known HAT, and human tumors. According to our previous studies, we found that MYST4 was overexpressed in ovarian high-grade serous carcinomas and patients with tumors overexpressing MYST4 had significantly worse survival. Therefore, we investigated whether MYST4 plays the same role in other cancers. Here we provide evidences that MYST4, may be involved in tumor cell growth and progression. By immunohistochemistry, we found that MYTS4 is highly expressesed in hepatocellular carcinomas (HCCs) and breast cancers than in normal tissues. Moreover, patients with HCCs overexpressing MYST4 had signigicantly worse survival. This is the first evidence suggesting that MYST4 may be involved in the progression of HCCs. In order to study the function of MYST4 in tumor cells, we used quantitative RT-PCR and selected several cancer cell lines including ovarian cancer cell line A2780, breast cancer cell line SKBR3 and hepatoma cell line Huh7 which expressed high levels of MYST4 and performed shRNA knockdown experiments. By cell proliferation assay and flow cytometry, we found that MYST4 enhanced cancer cell growth and regulated cell cycle progression. In addition, we observed that the migration distance was significantly decreased in MYST4 knockdown cell lines. This finding suggested that MYST4 promotes tumor migration. We performed microarray and found several target genes that were down-regulated by MYST4 knockdown, some may involved in cancer cell metastasis. Together, our study suggests that MYST4 promotes cancer cells growth and migration. Overexpression of MYST4 in cancer cells may induce tumors toward a more aggressive behavior.
|Appears in Collections:||病理學科所|
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