Silencing HOXD10 by promoter region hypermethylation activates ERK signaling in hepatocellular carcinoma.
Silencing HOXD10 by promoter region hypermethylation activates ERK signaling in hepatocellular carcinoma.
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通过启动子区域高甲基化沉默 HOXD10 可激活肝细胞癌中的 ERK 信号传导
DOI：
10.1186/s13148-017-0412-9
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发表时间：
2017
影响因子：
5.7
通讯作者：
Guo M
中科院分区：
文献类型：
--
作者：
Guo Y;Peng Y;Gao D;Zhang M;Yang W;Linghu E;Herman JG;Fuks F;Dong G;Guo M
研究背景肝细胞癌是全球第五大常见恶性肿瘤，也是全球第三大癌症相关死亡原因。HomeoboxD10(HOXD10)的失调被发现在不同的癌症类型中抑制或促进癌症的进展。方法收集117例原发性肝细胞癌标本、15例正常肝组织标本和13个肝癌细胞系(SNU182、SNU449、HBXF344、SMMC7721、Huh7、HepG2、LM3、PLC/PRF/5、BEL7402、SNU387、SNU475、QGY7703和Huh1)。采用甲基化特异性聚合酶链式反应、流式细胞术、免疫印迹、Transwell、siRNA和染色质免疫共沉淀等方法。HOXD10甲基化与血管癌栓、肿瘤细胞分化和3年总生存率显著相关(均P<0.05)。HOXD10基因的表达受启动子区域甲基化调控。HOXD10抑制肝癌细胞集落形成、细胞增殖、侵袭和迁移，并诱导G2/M期停滞和细胞凋亡。HOXD10抑制小鼠肝癌细胞移植瘤生长。HOXD10通过抑制ERK信号通路抑制肝癌生长。结论HOXD10在人肝细胞癌中存在频繁甲基化，其表达受启动子区甲基化调控。HOXD10在体内外均能抑制肝癌细胞的生长。HOXD10通过抑制ERK信号通路抑制人肝癌。
BackgroundHepatocellular 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).MethodsPrimary 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.ResultsHOXD10 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 (allP< 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.ConclusionHOXD10 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.
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影响因子：
8.8
作者：
Hakami, F.;Darda, L.;Stafford, P.;Woll, P.;Lambert, D. W.;Hunter, K. D.
通讯作者：
Hunter, K. D.
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
29.4
作者：
Revill K;Wang T;Lachenmayer A;Kojima K;Harrington A;Li J;Hoshida Y;Llovet JM;Powers S
通讯作者：
Powers S
影响因子：
--
作者：
Li X;Yu J;Brock MV;Tao Q;Herman JG;Liang P;Guo M
通讯作者：
Guo M
影响因子：
254.7
作者：
Siegel, Rebecca;Naishadham, Deepa;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin