CUL4B, NEDD4, and UGT1As involve in the TGF-β signalling in hepatocellular carcinoma.
CUL4B, NEDD4, and UGT1As involve in the TGF-β signalling in hepatocellular carcinoma.
复制标题
CUL4B、NEDD4 和 UGT1As 参与肝细胞癌中的 TGF-β 信号转导。
DOI：
10.5604/16652681.1203154
复制
发表时间：
2016
影响因子：
3.8
通讯作者：
Yubao Zhang
中科院分区：
文献类型：
--
作者：
Zhaowei Qu;Di Li;Haitao Xu;Rujia Zhang;Bing Li;Chengming Sun;W. Dong;Yubao Zhang
导言和目标
TGF-β信号通路参与了肝细胞癌（HCC）的发生和发展。因此，这项生物信息学研究旨在确定HCC细胞中TGF-β活化的潜在分子机制。
材料和方法
数据集GSE 10393从Gene Expression Omnibus下载，包括2个经TGF-β（100 pmol/L，48 h）处理的Huh-7（HCC细胞系）样本和2个未处理样本。使用Limma软件包筛选差异表达基因（DEG）（假发现率< 0.05，|log 2倍数变化|> 1.5），然后进行功能、途径和疾病的富集分析。此外，蛋白质-蛋白质相互作用（PPI）网络是基于来自多个数据库（包括INACT、MINT、BioGRID、UniProt、BIND、BindingDB和SPIKE数据库）的PPI数据构建的。使用来自ChEA数据库的转录因子（Tf）-DEG对（Bonferroni调整的p值< 0.01）和DEG-DEG对来构建TF-DEG调控网络。此外，通过整合DEG-DEG对、TF-DEG对和DEG-pathway对，构建了TF-pathway-DEG复合网络。
结果
共鉴定出209个DEG和30个TF。DEG在粘连相关功能方面显著丰富。PPI网络显示了中枢基因，如CUL 4和NEDD 4。根据TF-DEG调控网络，SMAD 2、SMAD 3和HNF 4A靶向两个枢纽基因。此外，TF-途径-DEG网络中的11条途径主要由UGT 1Afamily和CYP 3A 7富集，推测它们受SMAD 2、SMAD 3、SOX 2、TP 63和HNF 4A的调控。
结论
TGF-β可能通过SMAD 2/SMAD 3-NEDD 4、HNF 4A-CUL 4 B/NEDD 4、SOX 2/TP 63/HNF 4A-CYP 3A 7、SMAD 2/SMAD 3/SOX 2/TP 63/HNF 4A-UGT 1As等途径影响肝癌细胞的生物学过程。
INTRODUCTION AND AIM
TGF-β signalling is involved in pathogenesis and progress of hepatocellular carcinoma (HCC). This bioinformatics study consequently aims to determine the underlying molecular mechanism of TGF-β activation in HCC cells.
MATERIAL AND METHODS
Dataset GSE10393 was downloaded from Gene Expression Omnibus, including 2 Huh-7 (HCC cell line) samples treated by TGF-β (100 pmol/L, 48 h) and 2 untreated samples. Differentially expressed genes (DEGs) were screened using Limma package (false discovery rate < 0.05 and |log2 fold change| > 1.5), and then enrichment analyses of function, pathway, and disease were performed. In addition, protein-protein interaction (PPI) network was constructed based on the PPI data from multiple databases including INACT, MINT, BioGRID, UniProt, BIND, BindingDB, and SPIKE databases. Transcription factor (Tf)-DEG pairs (Bonferroni adjusted p-value < 0.01) from ChEA database and DEG-DEG pairs were used to construct TF-DEG regulatory network. Furthermore, TF-pathway-DEG complex network was constructed by integrating DEG-DEG pairs, TF-DEG pairs, and DEG-pathway pairs.
RESULTS
Totally, 209 DEGs and 30 TFs were identified. The DEGs were significantly enriched in adhesion-related functions. PPI network indicted hub genes such as CUL4Band NEDD4. According to the TF-DEG regulatory network, the two hub genes were targeted by SMAD2, SMAD3, and HNF4A. Besides, the 11 pathways in TF-pathway-DEG network were mainly enriched by UGT1Afamily and CYP3A7, which were predicted to be regulated by SMAD2, SMAD3, SOX2, TP63, and HNF4A.
CONCLUSIONS
TGF-β might influence biological processes of HCC cells via SMAD2/SMAD3-NEDD4, HNF4A-CUL4B/NEDD4, SOX2/TP63/HNF4A-CYP3A7, and SMAD2/SMAD3/SOX2/TP63/HNF4A-UGT1As regulatory pathways.
影响因子：
4.1
作者：
Kuratomi, G;Komuro, A;Imamura, T
通讯作者：
Imamura, T
影响因子：
5.2
作者：
Ryouichi Tsunedomi;N. Iizuka;Y. Hamamoto;S. Uchimura;Takanobu Miyamoto;T. Tamesa;Toshimasa Okada;N. Takemoto;M. Takashima;Kazuhiko Sakamoto;K. Hamada;H. Yamada‐Okabe;M. Oka
通讯作者：
Ryouichi Tsunedomi;N. Iizuka;Y. Hamamoto;S. Uchimura;Takanobu Miyamoto;T. Tamesa;Toshimasa Okada;N. Takemoto;M. Takashima;Kazuhiko Sakamoto;K. Hamada;H. Yamada‐Okabe;M. Oka
影响因子：
13.5
作者：
Yasui, K;Arii, S;Inazawa, J
通讯作者：
Inazawa, J