Project description:Liver cancer, including hepatocellular carcinoma (HCC), is a malignant tumor type with high metastasis and mortality rate in worldwide. Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and associated with the pathogenesis of several cancers, while its biological functions and molecular targets in HCC are not clear. In this study, we overexpressed USF1 in Huh7 cells and used whole transcriptome profile sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) methods to systematically investigate the downstream targets of USF1. Following polymerase chain reaction (PCR) was used to validate the downstream targets. Based on the results, we found USF1 significantly regulated 350 differentially expressed genes (DEGs). Up DEGs were mainly protein coding genes, and enriched in immune and inflammation response pathways; while down DEGs were mainly lncRNAs, indicating the regulatory feature of USF1. We also detected USF1 directly bound to the promoter region of 2492 genes, which may deeply participate in the viral progression and cell proliferation pathways. By integrating these two datasets, we detected 16 overlapped genes, including down lncRNA-NEAT1 and up TF-ETV5. Down lncRNA-NEAT1 showed reverse expression pattern and prognosis result to USF1 in liver cancer patients, while up TF-ETV5 showed consistent result to USF1. Promoter region motif analysis indicated that ETV5 had more binding motifs and genes than USF1 itself for USF1-regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. Finally, we validated the direct interaction between USF1 and the promoter of ETV5 using ChIP-qPCR. In summary, our results demonstrated that USF1 binds to the promoter region of thousands of genes, and affects large part of DEGs by indirectly manner. The downstream genes, including lncRNA-NEAT1 and TF-ETV5, may also tightly participate in the regulated network by USF1 and have potential functions in the progression of HCC. The USF1 and its downstream targets could be used as potential targets for HCC therapy in future.

Project description:Liver cancer, including hepatocellular carcinoma (HCC), is a malignant tumor that has high rates of metastasis and mortality worldwide. Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and is associated with the pathogenesis of several cancers, but its biological functions and molecular targets in HCC remain unclear. Huh7 cells that overexpress USF1 were used with whole transcriptome profiling through RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing methods to investigate the downstream targets of USF1. Reverse transcription-quantitative PCR was then used to validate the downstream targets. The results showed that USF1 significantly regulates 350 differentially expressed genes (DEGs). The upregulated DEGs were primarily protein-coding genes enriched in immune and inflammation response pathways, while the downregulated DEGs were mainly coding long non-coding (lnc)RNAs, indicating the regulatory function of USF1. It was also demonstrated that USF1 directly binds to the promoter region of 2,492 genes, which may be involved in the viral progression and cell proliferation pathways. By integrating these two datasets, 16 overlapped genes were detected, including downregulated lncRNA-NEAT1 and upregulated TF-ETV5. The downregulated lncRNA-NEAT1 showed reverse expression pattern and prognosis result compared with that of USF1 in patients with liver cancer, while upregulated TF-ETV5 showed consistent results with USF1. Promoter region motif analysis indicated that ETV5 has more binding motifs and genes than USF1 itself for USF1-regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. The study also validated the direct interaction between USF1 and the promoter of ETV5 using ChIP-qPCR. In summary, the results demonstrated that USF1 binds to the promoter region of thousands of genes and affects a large part of DEGs indirectly. Downstream genes, including lncRNA-NEAT1 and TF-ETV5, may also have potential functions in the regulated network by USF1 and have potential functions in the progression of HCC. The present findings suggested that USF1 and its downstream targets could be potential targets for HCC therapy in the future.

			Action	DRS
	SRR24504133_1.fastq.gz	Fastqsanger.gz
	SRR24504133_2.fastq.gz	Fastqsanger.gz
	SRR24504134_1.fastq.gz	Fastqsanger.gz
	SRR24504134_2.fastq.gz	Fastqsanger.gz
	SRR24504135_1.fastq.gz	Fastqsanger.gz

Dataset Information

USF1 modulates transcription and cellular functions by regulating multiple transcription factors in Huh7 cells.

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