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Objective:The aim of the study is to screen transcription factor genes related to the prognosis of adult patients with sepsis. Methods:Twenty-three patients with sepsis and 10 healthy individuals admitted for RNA-seq. Differential factors were enriched by four transcription factor databases, and survival analysis was adopted for core factors. Then, target genes were submitted to STRING to constitute the protein-protein interaction network. Single-cell technology was used to localize cell lines. Finally, a transcription-target gene regulation network was constituted. Results:A total of 4,224 differentially expressed genes were obtained between sepsis and normal control groups. Protein-protein interaction results showed that FOXO3, NFKB1, SPI1, STAT5A, and PPARA were located in the center of the network. Target genes were related to cytokine-mediated signaling pathway and transcription regulator activity, etc. SPI1 was mainly located in monocyte cell lines, while FOXO3, PPARA, SP1, STAT3, and USF1 were expressed in monocyte cell lines, NK-T cell lines, and B cell lines. Compared with those in the control group, FOXO3, SP1, SPI1, STAT3, and USF1 were highly expressed in the sepsis group, while PPARA had low expression. Conclusions:Transcription factors, such as FOXO3, PPARA, SP1, SPI1, STAT3, and USF1, are correlated with the prognosis of sepsis patients and thus may have a potential research value. Clinical Trial Registration:The clinical trial registration number is ChiCTR1900021261.

Targeting cytokinesis can suppress tumor growth by blocking cell division and promoting apoptosis. We aimed to characterize key cytokinesis regulator in hepatocellular carcinoma (HCC) progression, providing insights into identifying promising HCC therapeutic targets. The unbiased bioinformatic screening identified Anillin actin binding protein (ANLN) as a critical cytokinesis regulator involved in HCC development. Functional assay demonstrated that knockdown of ANLN inhibited HCC growth by inducing cytokinesis failure and DNA damage, leading to multinucleation and mitotic catastrophe. Mechanistically, ANLN acts as a scaffold to strengthen interaction between RACGAP1 and PLK1. ANLN promotes PLK1-mediated RACGAP1 phosphorylation and RhoA activation to ensure cytokinesis fidelity. To explore the function of ANLN in HCC tumorigenesis, we hydrodynamically transfected c-Myc and NRAS plasmids into Anln+/+, Anln+/−, and Anln−/−mice through tail vein injection. Hepatic Anlnablation significantly impaired c-Myc/NRAS-driven hepatocarcinogenesis. Moreover, enhanced hepatic polyploidization was observed in Anlnablation mice, manifesting as increasing proportion of cellular and nuclear polyploidy. Clinically, ANLN is upregulated in human HCC tissues and high level of ANLN is correlated with poor patients’ prognosis. Additionally, the proportion of cellular polyploidy decreases during HCC progression and ANLN level is significantly correlated with cellular polyploidy proportion in human HCC samples. In conclusion, ANLN is identified as a key cytokinesis regulator contributing to HCC initiation and progression. Our findings revealed a novel mechanism of ANLN in the regulation of cytokinesis to promote HCC tumorigenesis and growth, suggesting targeting ANLN to inhibit cytokinesis may be a promising therapeutic strategy for HCC.

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