Linc-smad7通过靶向miR-125b/SIRT1轴促进胰腺癌细胞迁移和侵袭  

Linc-smad7 promotes migration and invasion of pancreatic cancer cells by targeting miR-125b/SIRT1 axis

作　　者：韩丽丽 段文姣 周维肖 张淑群[1] HAN Lili;DUAN Wenjiao;ZHOU Weixiao;ZHANG Shuqun(Hospital of Tumor,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China;Department of Clinical Laboratory,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China)

机构地区：[1]西安交通大学第二附属医院肿瘤病院,陕西西安710004 [2]西安交通大学第二附属医院检验科,陕西西安710004

出　　处：《西安交通大学学报（医学版）》2024年第1期112-118,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省自然科学基金资助项目(青年项目)(No.2019JQ-128)。

摘　　要：目的探讨长链非编码RNA smad7(long non-coding RNA smad7,Linc-smad7)对胰腺癌(pancreatic cancer,PC)细胞侵袭、迁移的作用及其作用机制。方法qRT-PCR检测PC组织及细胞系中Linc-smad7的表达;Transwell小室观察过表达Linc-smad7对PaCa-2细胞迁移、侵袭能力的影响;荧光素酶报告基因检测Linc-smad7对miR-125b,以及miR-125b对沉默调节蛋白1(Sirtuin1,SIRT1)的结合作用;qRT-PCR检测Linc-smad7在PaCa-2细胞中对miR-125b表达的调控作用,qRT-PCR、Western blotting检测miR-125b对SIRT1表达的调控作用。结果Linc-smad7在PC组织及细胞系中明显升高;Linc-smad7表达上调的PaCa-2细胞迁移、侵袭能力增强,miR-125b表达下降;miR-125b表达上调后,SIRT1表达显著下降;荧光素酶报告基因结果提示Linc-smad7直接靶向结合miR-125b,miR-125b直接结合SIRT1;过表达Linc-smad7或是下调miR-125b表达可逆转SIRT1沉默对PaCa-2细胞侵袭、迁移能力的影响。结论Linc-smad7通过miR-125b/SIRT1轴促进PaCa-2细胞侵袭和迁移。Objective To explore the role of long non-coding RNA smad7(Linc-smad7)in invasion and migration of pancreatic cancer(PC)cells and its mechanisms.Methods The expression level of Linc-smad7 in PC tissues and cell lines was detected by qRT-PCR assays.Transwell assays were performed to observe the effect of Linc-smad7 overexpression on the migration and invasion abilities of PaCa-2 cells.Luciferase reporter analysis was made to detect the direct binding effect of Linc-smad7 on miR-125b and miR-125b on Sirtuin1(SIRT1).qRT-PCR assays were used to detect the regulatory effect of Linc-smad7 on miR-125b expression in PaCa-2 cells.qRT-PCR and Western blotting assays were used to detect the regulatory effect of miR-125b on SIRT1 expression.Results Linc-smad7 was significantly increased in PC tissues and cell lines.Paca-2 cells with overexpressed Linc-smad7 showed higher migration and invasion abilities,while miR-125b expression was decreased.After the expression of miR-125b was increased,the expression of SIRT1 was decreased significantly.Luciferase reporter assays results suggested that Linc-smad7 directly targeted with miR-125b,and miR-125b directly bound with SIRT1.Increased Linc-Smad7 or decreased miR-125b could reverse the effect of SIRT1 inhibition on invasion and migration of PaCa-2 cells.Conclusion Linc-smad7 promotes invasion and migration of PaCa-2 cells through miR-125b/SIRT1 axis.

关 键 词：胰腺癌 长链非编码RNA smad7(Linc-smad7) miR-125b 迁移 侵袭 

分 类 号：R735.7[医药卫生—肿瘤]