MYB Proto-oncogene-like 1-TWIST1 Axis Promotes Growth and Metastasis of Hepatocellular Carcinoma Cells
MYB Proto-oncogene-like 1-TWIST1 Axis Promotes Growth and Metastasis of Hepatocellular Carcinoma Cells
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MYB原癌基因样1-TWIST1轴促进肝细胞癌细胞的生长和转移
DOI：
10.1016/j.omto.2020.05.016
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发表时间：
2020-06
影响因子：
5.7
通讯作者：
Li Heping
中科院分区：
文献类型：
--
作者：
Xie Binhui;Liu Yao;Zhao Zhenxian;Liu Qingquan;Wang Xiaonong;Xie Yuankang;Liu Yanhong;Liu Yuwen;Yang Yan;Long Jianting;Dai Qiangsheng;Li Heping
MYB类原癌基因1(MYBL1)是一种强大的转录激活因子，在肿瘤的发生发展中起重要作用。然而，MYBL1在肝细胞癌中的确切生物学功能和分子机制尚不清楚。在本研究中，我们发现MYBL1分别在肝细胞癌细胞系和肝细胞癌标本中显著过表达。此外，在368例人肝细胞癌组织样本中，MYBL1的表达与肿瘤进展呈正相关，与患者生存呈负相关。体内实验表明，MYBL1基因过表达，MYBL1基因表达下调，肝癌细胞在体内增殖和转移。此外，我们还发现MYBL1高表达的肝细胞癌患者较低MYBL1表达的患者总体生存时间更短，无病生存期更差。MYBL1通过直接靶向Twist1启动子在转录水平上调Twist1的表达。更重要的是，体外分析与在大量人类肝癌样本中观察到的MYBL1和Twist1表达之间的显著相关性是一致的。综上所述，我们的结果表明MYBL1在肝癌的生长和转移中起重要作用，并揭示了Twist1在肝癌中上调的可能机制。
MYB proto-oncogene-like 1 (MYBL1) has been reported to be a strong activator of transcription and plays an important role in the development of cancer. However, the precise biological function and molecular mechanism of MYBL1 in hepatocellular carcinoma (HCC) cells remain unclear. In the present study, we found that the expression of MYBL1 was markedly overexpressed in HCC cell lines and HCC samples, respectively. Moreover, MYBL1 expression positively correlated with tumor progression and inversely correlated with patient survival in 368 human HCC tissue samples. Overexpression of MYBL1 induced, whereas knockdown of MYBL1 reduced, HCC proliferation and metastasis bothin vitroandin vivo. Furthermore, we demonstrated that HCC patients with high MYBL1 expression had significantly shorter overall and poorer disease-free survival than those with low MYBL1 expression. MYBL1 transcriptionally upregulated TWIST1 expression by directly targeting the TWIST1 promoter. More importantly, thein vitroanalysis was consistent with the significant correlation between MYBL1 and TWIST1 expression observed in a large cohort of human HCC specimens. Taken together, our results demonstrate that MYBL1 plays an important role in HCC growth and metastasis and reveal a plausible mechanism for upregulation of TWIST1 in HCC.
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影响因子：
2
作者：
Goodwin CR;Yanamadala V;Ruiz-Valls A;Abu-Bonsrah N;Shankar G;Sankey EW;Boone C;Clarke MJ;Bilsky M;Laufer I;Fisher C;Shin JH;Sciubba DM
通讯作者：
Sciubba DM
影响因子：
--
作者：
Ghouri YA;Mian I;Rowe JH
通讯作者：
Rowe JH
影响因子：
13.5
作者：
Giannini, Edoardo G.;Farinati, Fabio;Trevisani, Franco
通讯作者：
Trevisani, Franco
影响因子：
64.5
作者：
Yang, J;Mani, SA;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
2.2
作者：
Brabender, J;Lord, RV;Danenberg, PV
通讯作者：
Danenberg, PV