探究CUL4B在结直肠癌患者来源的肿瘤类器官中调控miRNAs  

Exploration of the Regulation of miRNAs by CUL4B in Colorectal Cancer Patient-derived Tumor Organoids

作　　者：李彦军 王宇星 穆雅琴 鲍欣雨 刘杨青 何耀麒 肖冰帅 杨嘉凯 张年萍 郝大江[3] LI Yan-jun;WANG Yu-xing;MU Ya-qin;BAO Xin-yu;LIU Yang-qing;HE Yao-qi;XIAO Bing-shuai;YANG Jia-kai;ZHANG Nian-ping;HAO Da-jiang(Institute of Immunology of Medical School,Shanxi Datong University,Datong Shanxi,037009;School of Basic Medicine,Shandong University,Jinan Shandong,250012;The Third People's Hospital of Datong,Datong Shanxi,037046)

机构地区：[1]山西大同大学医学院免疫学研究所,山西大同037009 [2]山东大学基础医学院,山东济南250012 [3]大同市第三人民医院,山西大同037008

出　　处：《山西大同大学学报（自然科学版）》2023年第2期67-72,共6页Journal of Shanxi Datong University(Natural Science Edition)

基　　金：山西省基础研究计划青年项目[20210302123338];山西省高等学校科技创新项目[2021L372];山西省大学生创新创业训练计划项目[20220790];山西大同大学博士科研启动项目;山西大同大学产学研项目[2022019];山西大同大学大学生创新创业项目[XDC2021115和和XDC2022109]。

摘　　要：目的探究CUL4B在肿瘤患者来源的结直肠癌肿瘤类器官中调控miRNAs。方法利用干扰CUL4B的和其对照的PDOs样本,进行miRNA-seq,对差异miRNAs的靶基因进行KEGG和GO等分析。利用TargetScan和miRDB 2个数据库分别预测可能受CUL4B调控的并且评分≥85分的miRNAs,结合miRNA-seq差异miRNAs进行韦恩分析。结果miRNA-seq结果显示共有41个差异miRNAs。TargetScan和miRDB两个数据库和测序数据韦恩分析发现miR495-3p、miR381-3p和miR148b-5p 3个共同交集的miRNAs。KEGG结果显示代谢通路富集的基因个数最多,溶酶体富集基因Q值最小。GO分析结果显示单有机体过程、蛋白质结合和细胞质富集基因最多。流式细胞仪检测发现干扰CUL4B的表达并不影响PDOs的细胞周期。结论CUL4B可能是通过代谢通路和溶酶体2个信号通路调控miR495-3p、miR381-3p和miR148b-5p。Objective To explore the regulation of miRNAs by CUL4B in colorectal cancer patient-derived tumor organoids.Methods Using patient-derived organoids(PDOs)samples that knockdown of CUL4B and its controls,miRNA-seq was performed,and target genes of differential miRNAs were analyzed by KEGG and GO.Two databases,TargetScan and miRDB,were used to predict miRNAs that may be regulated by CUL4B and score≥85 points,respectively,and differential miRNAs of miRNAseq were combined to perform a Venn analysis.Results miRNA-seq results showed a total of 41 differential miRNAs.TargetScan and miRDB databases,and sequencing data Venn analysis found miR495-3p,miR381-3p and miR148b-5p.The KEGG results showed that the number of genes enriched in metabolic pathways was the largest,and the Q value of genes enriched in lysosomes was the smallest.GO analysis showed that single-organism process,protein binding and cytoplasm were the most enriched genes.Flow cytometry showed that knockdown of CUL4B did not affect the cell cycle of PDOs.Conclusion CUL4B may regulate miR495-3p,miR381-3p and miR148b-5p through metabolic pathways and lysosome signaling pathways.

关 键 词：CUL4B 结直肠癌 肿瘤类器官 MIRNAS 

分 类 号：R735.1[医药卫生—肿瘤]