Serine protease inhibitor Hespintor’s potential mechanism based on integrated transcriptomics in inhibiting the growth of transplanted hepatoma in nude mice / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To investigate the relationship between differential expressions of lncRNAs and mRNAs and Hespintor’s possible anti-tumor mechanism using transcriptome sequencing technology. 【Methods】 First， a nude mouse model of human hepatoma tumors was established. The tumor tissue mass was collected after 4 weeks of group treatment. The cDNA libraries of tumor tissues were established in the Hespintor treatment group and the solvent control group， and transcriptome sequencing was performed. Based on RNA-seq data， the differentially expressed lncRNA and mRNA genes were screened， and the functional enrichment and interaction analysis were performed. The network module division approach was utilized to identify the target genes of Hespintor and build its regulatory network. 【Results】 The Hespintor treatment group yielded a high-confidence differentially expressed gene collection of 2 003 lncRNAs （DEGs lncRNA） and 1 038 mRNAs （DEGs mRNA）. Target mRNAs regulated by DEGs lncRNA were mainly enriched in PIP3 to activate the Akt signal， p53 signal pathway， FOXO-mediated transcription， and cell cycle， among other things. DEGs mRNA were primarily enriched in chemokine signaling pathways， extracellular matrix receptor interactions， complement， and coagulation cascades. Both of them were related in three ways： cell behavior， transcriptional regulation， and cell cycle. 【Conclusion】 The PI3K/Akt signaling pathway may play a key role in the inhibitory effect of Hespintor on tumor， inducing G1/S phase cell cycle arrest and apoptosis.