Bioinformatic Analysis and In Vitro and In Vivo Experiments Reveal That Fibrillarin Participates in the Promotion of Lung Metastasis in Hepatocellular Carcinoma.
Bioinformatic Analysis and In Vitro and In Vivo Experiments Reveal That Fibrillarin Participates in the Promotion of Lung Metastasis in Hepatocellular Carcinoma.
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DOI：
10.3390/bioengineering9080396
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发表时间：
2022-08-17
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影响因子：
--
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肺转移是肝细胞癌最常见的转移方式，是影响预后的重要因素。然而，肝细胞癌肺转移的机制仍不清楚。为了探讨这些机制，首次采用加权基因共表达网络分析（WGCNA）技术寻找与肺转移相关的枢纽基因。通过蛋白质相互作用网络分析，我们获得了67个与肝细胞癌肺转移相关的基因，这些基因主要与核糖体途径和功能有关，其中纤维蛋白（fibrillarin，FBL）可能是一个重要的中枢基因。此外，我们发现FBL在肝细胞癌中高表达，其高表达增加肺转移率并提示预后不良。敲低FBL基因可显著抑制肝癌细胞的增殖和干细胞化，并抑制肝癌细胞的迁移和侵袭。此外，我们发现FBL可能参与肝细胞癌中MYC和E2 F途径的调节。最后，我们证明了FBL的敲低可以抑制体内肝癌细胞的生长。总之，核糖体生物合成相关蛋白，尤其是Fibrillarin，在肝细胞癌肺转移中起重要作用。
Lung metastasis, the most frequent metastatic pattern in hepatocellular carcinoma, is an important contributor to poor prognosis. However, the mechanisms responsible for lung metastasis in hepatocellular carcinoma remain unknown. Aiming to explore these mechanisms, weighted gene coexpression network analysis (WGCNA) was firstly used to find hub genes related to lung metastasis. Then, we obtained 67 genes related to lung metastasis in hepatocellular carcinoma which were mainly related to ribosomal pathways and functions, and a protein interaction network analysis identified that fibrillarin (FBL) might be an important hub gene. Furthermore, we found that FBL is highly expressed in hepatocellular carcinoma and that its high expression increases the rate of lung metastasis and indicates a poor prognosis. Knockdown of FBL could significantly reduce proliferation and stemness as well as inhibiting the migration and invasion of hepatocellular carcinoma cells. Moreover, we found that FBL might be involved in the regulation of MYC and E2F pathways in hepatocellular carcinoma. Finally, we demonstrated that the knockdown of FBL could suppress hepatocellular carcinoma cell growth in vivo. In conclusion, ribosome-biogenesis-related proteins, especially Fibrillarin, play important roles in lung metastasis from hepatocellular carcinoma.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
6.2
作者：
Uchino, Koji;Tateishi, Ryosuke;Koike, Kazuhiko
通讯作者：
Koike, Kazuhiko
影响因子：
2.9
作者：
Zhang J;Yang G;Li Q;Xie F
通讯作者：
Xie F
DOI：
10.1016/s0140-6736(17)33326-3
发表时间：
2018-03-17
期刊：
Lancet (London, England)
影响因子：
--
作者：
Allemani C;Matsuda T;Di Carlo V;Harewood R;Matz M;Nikšić M;Bonaventure A;Valkov M;Johnson CJ;Estève J;Ogunbiyi OJ;Azevedo E Silva G;Chen WQ;Eser S;Engholm G;Stiller CA;Monnereau A;Woods RR;Visser O;Lim GH;Aitken J;Weir HK;Coleman MP;CONCORD Working Group
通讯作者：
CONCORD Working Group
影响因子：
56.9
作者：
Ebright, Richard Y.;Lee, Sooncheol;Micalizzi, Douglas S.
通讯作者：
Micalizzi, Douglas S.