文献类型：期刊文献

中文题名：熊果酸对甲状腺乳头状癌细胞LINC01089及其靶基因表达的影响

英文题名：Effect of Ursolic Acid on Expressions of LINC01089 and Its Target Genes in Thyroid Papillary Carcinoma Cells

作者：伊琳[1];何亚丽[1];吕红英[1];王晓科[1,2];杨鑫[1,2];顾远晖[1,2]

第一作者：伊琳

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃省人民医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2025

卷号：43

期号：9

起止页码：11

中文期刊名：中华中医药学刊

外文期刊名：Chinese Archives of Traditional Chinese Medicine

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(82160842);甘肃省自然科学基金项目(20JR10RA368,24JRRA590);甘肃省人民医院院内科研资金项目(23GSSYD-17)。

语种：中文

中文关键词：长链非编码RNA;甲状腺乳头状癌;熊果酸;基因

外文关键词：long chain non coding RNA;thyroid papillary carcinoma;ursolic acid;genes

摘要：目的分析熊果酸对甲状腺乳头状癌(Papillary thyroid carcinoma,PTC)长链非编码RNA(Long chain non coding RNA,lncRNA)-LINC01089及其靶基因表达的影响。方法LINC01089为前期通过转录组测序筛选并通过验证的差异表达lncRNA,体外常规培养甲状腺乳头状癌TPC-1细胞、正常人甲状腺细胞(Nthy-Ori3-1)。将细胞分为正常组(正常人甲状腺细胞组)、对照组(TPC-1细胞组)、不同浓度熊果酸(Ursolic acid,UA)干预组(10、20、40μmol·L^(-1))。CCK-8法检测各组甲状腺乳头状癌TPC-1细胞的存活率;划痕实验、Transwell实验检测不同浓度UA对TPC-1细胞水平、垂直迁移以及侵袭的影响作用;利用RT-qPCR法检测TPC-1细胞中LINC01089的相对表达量及熊果酸的干预作用;RT-qPCR及Western blot检测靶基因丝状伪足相关基因(Ras homolog family member F,RHOF)、4-羟基苯丙酮酸双加氧酶(4-Hydroxyphenylpyruvate dioxygenase,HPD)的mRNA及蛋白表达水平以及熊果酸的干预作用。结果不同浓度的UA(10、20、40、80μmol·L^(-1))作用不同时间(12~48 h)后均能抑制TPC-1细胞的增殖,当UA浓度为10~40μmol·L^(-1)时,在12~24 h内随着浓度的增加和作用时间的延长,细胞的抑制效应逐渐增强,差异具有统计学意义(P<0.05),UA处理TPC-1细胞24 h后,细胞增殖缓慢,随着UA(10、20、40μmol·L^(-1))浓度的增高,细胞出现凋亡的形态学改变;与对照组相比,UA(10、20、40μmol·L^(-1))组可抑制TPC-1细胞迁移和侵袭,呈明显浓度依赖性,差异具有统计学意义(P<0.01)。熊果酸能不同程度上调LINC01089的表达量,下调RHOF、HPD的mRNA及蛋白表达水平。结论熊果酸对甲状腺乳头状癌细胞具有一定的抑制作用,其机制可能通过上调LINC01089作用于靶基因RHOF发挥抑癌效应。
Objective To analyze the effect of ursolic acid on the expressions of long chain non coding RNA(lncRNA)-LINC01089 and its target genes in papillary thyroid carcinoma(PTC).Method LINC01089 was a differentially expressed lncRNA that was previously screened and verified by transcriptome sequencing in the early stage.TPC-1 cells and normal human thyroid cells(Nthy-ori3-1)were routinely cultured in vitro and were divided into normal human thyroid cell group,control group and UA groups(10,20,40μmol·L^(-1)).The survival rate of TPC-1 cells in each group was detected by CCK-8 assays.Scratch and Transwell experiments were conducted to investigate the effects of different concentrations of ursolic acid on the horizontal,vertical migration and invasion of TPC-1 cells.RT qPCR method was used to detect the relative expression level of LINC01089 in TPC-1 cells and the intervention effect of ursolic acid.RT-qPCR and Western blot were used to detect the mRNA and pro-tein expression levels of target genes Ras Homolog Family Member F(RHOF)and 4-Hydroxyphenylpyruvate Dioxygenase(HPD)as well as the intervention effect of ursolic acid.Results Different concentrations of UA(10,20,40 and 80μmol·L^(-1))could inhibit the proliferation of TPC-1 cells for different periods of time(12~48 hours).When the concentration of ursolic acid was 10~40μmol·L^(-1),the inhibitory effect of the cells gradually increased with increasing of concentration and prolonga-tion of action time within 12 and 24 hours(P<0.05).After treating TPC-1 cells with ursolic acid for 24 hours,the cell prolif-eration was slow,and as the concentration of ursolic acid(10,20 and 40μmol·L^(-1))increased,morphological changed in cell apoptosis.Compared with the control group,the ursolic acid(10,20,40μmol·L^(-1))groups inhibited the migration and invasion of TPC-1 cells in a significant concentration dependent manner(P<0.01).Ursolic acid can up-regulate the expression of LINC01089,and down-regulate the mRNA and protein expression levels of RHOF and HPD.Conclusion Ursolic acid has a cer-tain inhibitory effect on thyroid papillary carcinoma cells,and its mechanism may be related with the LINC01089 and its target gene RHOF.