摘要
目的研究前列腺癌相关转录因子4(PCAT4)通过海绵化miR-508-5p上调细胞增殖上调节因子(URGCP)表达对乳腺癌进展的驱动作用。方法通过癌症基因组图谱分析乳腺癌组织中具有差异表达的lncRNA和miRNA的微阵列数据。实时荧光定量聚合酶链反应(RT-qPCR)评估乳腺癌中PCAT4表达。MTT和集落形成实验测定细胞增殖能力,TUNEL法分析细胞凋亡情况,Transwell实验分析细胞迁移和侵袭变化。RNA下拉和双荧光素酶测定分析PCAT4与miR-508-5p,以及miR-508-5p与URGCP的相关性。肿瘤异种移植研究分析PCAT4/miR-508-5p/URGCP轴与体内乳腺癌细胞生长的相关性。计量资料以均数±标准差(x±s)表示,两组间比较采用t检验,多组间比较采用单因素方差分析。Pearson相关性分析评价PCAT4和URGCP与miR-508-5p表达的相关性。结果乳腺癌组织和细胞中PCAT4的表达水平上调。敲除PCAT4能够抑制细胞增殖和转移,促进细胞凋亡。miR-508-5p是PCAT4的靶点,且与PCAT4呈负相关。乳腺癌中miR-508-5p过度表达可抑制细胞生长、迁移和侵袭,促进细胞凋亡。URGCP是miR-508-5p的靶点,可诱导乳腺癌的进展。肿瘤异种移植研究显示,PCAT4通过影响miR-508-5p/URGCP驱动乳腺癌进展。结论乳腺癌组织和细胞中PCAT4表达升高,PCAT4可以作为miR-508-5p的分子海绵,并通过激活URGCP蛋白表达显著促进乳腺癌进展。
Objective To investigate the driving effect of prostate cancer associated transcript 4(PCAT4)on the up-regulation of upregulator of cell proliferation(URGCP)expression in breast cancer progression through sponging miR-508-5p.Methods The microarray data of lncRNA and miRNA with differential expression in breast cancer tissue were analyzed by Cancer Genome Atlas.The expression of PCAT4 in breast cancer was evaluated by real-time quantitative polymerase chain reaction(RT-qPCR).Cell proliferation was measured by MTT and colony formation,cell apoptosis was analyzed by TUNEL,and cell migration and invasion were analyzed by Transwell.The correlation between PCAT4 and miR-508-5p,and miR-508-5p and URGCP was analyzed by RNA pull-down and double luciferase assay.Tumor xenograft studies were performed to analyze the correlation between PCAT4/miR-508-5p/URGCP axis and breast cancer cell growth in vivo.Measurement data were expressed as mean±standard deviation(x±s).T-test was used for comparison between two groups,and one-way analysis of variance was used for comparison between multiple groups.The correlation between PCAT4 and URGCP and miR-508-5p expression was evaluated by Pearson correlation analysis.Results The expression level of PCAT4 was up-regulated in breast cancer tissues and cells.Knockout of PCAT4 inhibited cell proliferation and metastasis and promoted cell apoptosis.miR-508-5p was the target of PCAT4 and was negatively correlated with PCAT4.Overexpression of miR-508-5p in breast cancer can inhibit cell growth,migration and invasion,and promote cell apoptosis.URGCP is the target of miR-508-5p and induces progression of breast cancer.Tumor xenograft studies showed that PCAT4 drives breast cancer progression by affecting miR-508-5p/URGCP.Conclusion The expression of PCAT4 is up-regulated in breast cancer tissues and cells,and PCAT4 can act as a molecular sponge of miR-508-5p,and significantly promote breast cancer progression by activating URGCP protein expression.
作者
冯东旭
张美峰
吴炜
王军
高平发
胡刚峰
施丽娟
陈大伟
李文兵
Feng Dongxu;Zhang Meifeng;Wu Wei;Wang Jun;Gao Pingfa;Hu Gangfeng;Shi Lijuan;Chen Dawei;Li Wenbing(Department of Nail and Breast Surgery,Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences,Shanghai 202150,China;Department of General Surgery,Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences,Shanghai 202150,China)
出处
《国际外科学杂志》
2023年第6期401-406,F0003,F0004,共8页
International Journal of Surgery
基金
上海市崇明区"可持续发展科技创新行动计划"项目(CKY2021-17)。
作者简介
通信作者:张美峰,Email:womenaifengfeng@163.com。
