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首页> 外文期刊>Clinical epigenetics. >Silencing HOXD10 by promoter region hypermethylation activates ERK signaling in hepatocellular carcinoma
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Silencing HOXD10 by promoter region hypermethylation activates ERK signaling in hepatocellular carcinoma

机译：通过启动子区域高甲基化沉默HOXD10激活肝细胞癌中的ERK信号传导

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class="Heading">Background id="Par1" class="Para">Hepatocellular carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. Dysregulation of HomeoboxD10 (HOXD10) was found to suppress or promote cancer progression in different cancer types. The function and regulation of HOXD10 remain unclear in human hepatocellular carcinoma (HCC). class="Heading">Methods id="Par2" class="Para">Primary HCC samples (117), normal liver tissue samples (15), and 13 HCC cell lines (SNU182, SNU449, HBXF344, SMMC7721, Huh7, HepG2, LM3, PLC/PRF/5, BEL7402, SNU387, SNU475, QGY7703, and Huh1) were included in this study. Methylation-specific PCR, flow cytometry, western blot, transwell, siRNA, and chromatin immunoprecipitation assays were employed. class="Heading">Results id="Par3" class="Para">HOXD10 was methylated in 76.9% (90/117) of human primary HCC samples. HOXD10 methylation was significantly associated with vessel cancerous embolus, tumor cell differentiation, and the 3-year overall survival rate (all P????0.05). The expression of HOXD10 was regulated by promoter region methylation. HOXD10 suppressed colony formation, cell proliferation, cell invasion and migration, and induced G2/M phase arrest and apoptosis in HCC cells. HOXD10 suppressed HCC cell xenograft growth in mice. HOXD10 suppresses HCC growth by inhibiting ERK signaling. class="Heading">Conclusion id="Par4" class="Para">HOXD10 is frequently methylated in human HCC, and the expression of HOXD10 is regulated by promoter region methylation. HOXD10 suppresses HCC cell growth both in vitro and in vivo. HOXD10 suppresses human HCC by inhibiting ERK signaling.
机译：class =“ Heading”>背景 id =“ Par1” class =“ Para”>肝细胞癌是全球第五大最常见的恶性肿瘤，也是与癌症相关死亡的第三大主要原因。发现HomeoboxD10（HOXD10）的失调可以抑制或促进不同癌症类型的癌症进展。在人类肝细胞癌（HCC）中，HOXD10的功能和调控尚不清楚。 class =“ Heading”>方法 id =“ Par2” class =“ Para”>主要HCC样品（ 117），正常肝组织样本（15）和13种HCC细胞系（SNU182，SNU449，HBXF344，SMMC7721，Huh7，HepG2，LM3，PLC / PRF / 5，BEL7402，SNU387，SNU475，QGY7703和Huh1）在这个研究中。进行了甲基化特异性PCR，流式细胞术，western印迹，transwell，siRNA和染色质免疫沉淀测定。 class =“ Heading”>结果 id =“ Par3” class =“ Para “> HOXD10在76.9％（90/117）的人类原发性HCC样品中被甲基化。 HOXD10甲基化与血管癌栓，肿瘤细胞分化和3年总生存率显着相关（所有 P ?? <0.05）。 HOXD10的表达受到启动子区域甲基化的调节。 HOXD10抑制HCC细胞中的集落形成，细胞增殖，细胞侵袭和迁移，并诱导G2 / M期阻滞和凋亡。 HOXD10抑制了小鼠中HCC细胞异种移植的生长。 HOXD10通过抑制ERK信号传导抑制HCC的生长。 class =“ Heading”>结论 id =“ Par4” class =“ Para”> HOXD10在人类HCC中经常被甲基化，其表达HOXD10的表达水平受启动子区域甲基化的调节。 HOXD10在体外和体内均可抑制HCC细胞的生长。 HOXD10通过抑制ERK信号传导抑制人类HCC。

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