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Gene regulatory network analysis on snRNAseq revealed key regulators for hepatocellular carcinoma progression

GSE278324 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/09/26 Platform GPL24676
Summary
Many clinical researchers have developed targeted therapy and immunotherapy for the case of advanced stage of hepatocellular carcinoma (HCC). However, the molecular mechanisms of HCC development still need to be investigated to improve the response rate of those therapies. Here, we generated single nucleus RNA sequencing (snRNAseq) data from biopsy samples of six patients with Barcelona Clinic Liver Cancer (BCLC) advanced C stage. We first found that the gene expression heterogeneity in hepatocytes was mainly dissected by vascular invasion. To identify the key regulators of malignant progression of hepatocytes, we applied TENET, a gene regulatory network (GRN) inference tool based on pseudotime-ordered single cell expression. TENET predicts that MLXIPL and CUX1 are the top two regulators and regulate each other. This prediction was comprehensively validated by overexpression and knockdown of CUX1 in two HCC cell lines. This study suggested that GRN analysis with single cell transcriptomics provides new therapeutic targets for HCC.
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Direct links to NCBI, no account and no request form: the whole study as GSE278324_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1166642 and SRA study SRP535461. Searching any of these in the dataset finder brings you back here.

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