摘要
目的探讨长链非编码RNA(long non-coding RNA,LncNA)FAM83H-AS1靶向结合微小RNA(microRNA,miR)-203调控krüppel样因子5(krüppel-like factor 5,KLF5)在子宫内膜癌细胞生长以及凋亡中的作用机制。方法采用在线生物信息学网站对FAM83H-AS1的下游靶向miRNA进行筛选和预测,筛选到miR-203,继续对miR-203的下游靶向mRNA进行筛选和预测,筛选到KLF5;使用双荧光素酶实验检测miR-203与LncRNA FAM83H-AS1以及KLF5的结合关系;将稳定低表达FAM83H-AS1的HEC-1A和HEC-1B细胞接种在裸鼠的体内进行动物学实验验证,建立人类子宫内膜癌异种移植的小鼠实验模型,测量移植肿瘤的增殖情况。结果FAM83H-AS1主要定位在细胞质内,双荧光素酶实验提示FAM83H-AS1与miR-203具有靶向结合关系,miR-203可以与KLF5 mRNA 3’-UTR序列靶向结合;低表达FAM83H-AS1的HEC-1A和HEC-1B细胞在体内的增殖速率明显降低,而且裸鼠异植体肿瘤重量也明显低于对照组;子宫内膜癌细胞在体外的增殖被miR-203 mimic抑制,敲减KLF5可以抑制子宫内膜癌细胞在体外的增殖。结论LncRNA FAM83H-AS1作为竞争性内源RNA吸附miR-203,从而释放KLF5,促进KLF5的表达,导致子宫内膜癌的发生与发展。
Objective To investigate the underlying mechanisms by which the long non-coding RNA(LncNA)FAM83H-AS1 targets microRNA(miR)-203 to regulate krüppel-like factor 5(KLF5)in the proliferation and apoptosis of endometrial cancer cells.Methods Used an online bioinformatics website to screen and predict downstream targeted miRNAs of FAM83H-AS1,and identified miR-203.Continued to screen and predict downstream targeted mRNA of miR-203,and identified KLF5.Used dual luciferase assay to detect the binding relationship between miR-203 and LncRNA FAM83H-AS1 and KLF5.Inoculated HEC-1A and HEC-1B cells with stable low expression of FAM83H-AS1 into nude mice for animal experiments to establish a mouse model of human endometrial cancer xenograft and measure the proliferation of transplanted tumors.Results FAM83H-AS1 was mainly localized in the cytoplasm,and dual luciferase assayed suggest a targeted binding relationship between FAM83H-AS1 and miR-203,and miR-203 could target KLF5 mRNA 3'-UTR sequence.The proliferation rate of HEC-1A and HEC-1B cells with low expression of FAM83H-AS1 in vivo was significantly reduced,and the weight of xenograft tumors in nude mice was also significantly lower than that in the control group.The proliferation of endometrial cancer cells in vitro was inhibited by miR-203 mimic,and knocking down KLF5 could inhibit the proliferation of endometrial cancer cells in vitro.Conclusion LncRNA FAM83H-AS1 acts as a competitive endogenous RNA to adsorb miR-203,thereby releasing KLF5 and promoting its expression,leading to the occurrence and development of endometrial cancer.
作者
宋晓霞
张子规
席巍
张金磊
SONG Xiao-xia;ZHANG Zi-gui;XI Wei;ZHANG Jin-lei(Department of Gynecology,the Fifth Clinical Medical College of Henan University of Chinese Medicine,Zhengzhou People's Hospital,Zhengzhou 450000,China)
出处
《医药论坛杂志》
2025年第6期561-567,共7页
Journal of Medical Forum
基金
河南省科技发展计划(222102310488)
河南省医学科技攻关计划联合共建项目(LHGJ20220794)
郑州市医疗卫生领域科技创新指导计划项目(2024YLZDJH290)。
