基于整合转录组学分析丝氨酸蛋白酶抑制剂Hespintor抑制肝癌裸鼠移植瘤生长的潜在机制  

Serine protease inhibitor Hespintor’s potential mechanism based on integrated transcriptomics in inhibiting the growth of transplanted hepatoma in nude mice

作　　者：伦永志 孙杰 魏玲 刘奔[1] 董雯 潘凌鸿 LUN Yongzhi;SUN Jie;WEI Ling;LIU Ben;DONG Wen;PAN Linghong(Key Laboratory of Medical Microecology,Fujian Province University,School of Pharmacy and Medical Technology,Putian University,Putian 351100;Beijing Centre for Physical and Chemical Analysis,Beijing 100089,China)

机构地区：[1]莆田学院药学与医学技术学院医学微生态学福建省高校重点实验室,福建莆田351100 [2]北京市理化分析测试中心,北京100089

出　　处：《西安交通大学学报（医学版）》2022年第2期202-212,共11页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：福建省自然科学基金项目(No.2021J011100);2018年福建省高校新世纪优秀人才项目;莆田市科技计划项目(No.2017S2001)。

摘　　要：目的利用转录物组测序技术探寻差异表达长链非编码RNA(Long non-coding RNA,lncRNA)、mRNA与Hespintor抗肿瘤潜在机制的关联性。方法首先建立人肝癌裸鼠移植瘤模型,分组给药4周后取瘤体,分别构建Hespintor治疗组、溶剂对照组瘤组织cDNA文库并进行转录物组测序,基于RNA-seq数据筛选差异表达lncRNA、mRNA基因集,继而进行功能富集及相互作用分析,再利用网络模块划分方法寻找Hespintor作用靶点基因并构建调控网络。结果筛选获得Hespintor治疗组高可信度的差异表达基因集lncRNA(DEGs lncRNA)2003个和mRNA(DEGs mRNA)1038个,DEGs lncRNA调控靶mRNA主要富集于PIP3激活Akt信号、p53信号通路、FOXO介导的转录和细胞周期等功能,DEGs mRNA主要富集于趋化因子信号通路、细胞外基质受体相互作用、补体和凝血级联等功能,两者关联性侧重体现在细胞行为、转录调控和细胞周期等三方面。结论PI3K/Akt信号通路可能在Hespintor抑制肿瘤效应中发挥主导作用,诱导细胞周期阻滞于G1/S期并引起细胞凋亡。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 2003 lncRNAs(DEGs lncRNA)and1038 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 PI3 K/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.

关 键 词：Hespintor 晚期肝细胞癌 转录物组测序技术 长链非编码RNA 差异表达基因集 

分 类 号：R73‒362[医药卫生—肿瘤]