MiR-34a/SIRT1 Axis Modulating Therapeutic Effect of Olaparib on Pancreatic Cancer through Suppressing PARP1 and EMT

被引：0
|
作者：
Liu, Linxun [1 ]
Deng, Rubing [2 ]
Yang, Jinyu [1 ]
Ye, Chengjie [1 ]
Yang, Pei [3 ]
Zhang, LingFeng [4 ]
Shen, Binbin [5 ]
机构：
[1] Qinghai Prov Peoples Hosp, Dept Gen Surg, Xining 810000, Qinghai, Peoples R China
[2] Sichuan Univ, Peoples Hosp Longquanyi Dist 1, Gen Surg Dept, ChengduyWest China Longquan Hosp, Chengdu, Sichuan, Peoples R China
[3] Mianyang Cent Hosp, Dept Hepatobiliary Surg, Mianyang 621000, Sichuan, Peoples R China
[4] First Peoples Hosp Huaihua City, Dept Hepatobiliary Surg, Huaihua 418000, Hunan, Peoples R China
[5] Jiaxing Univ, Dept Gen Surg, Affiliated Hosp, Jiaxing 314000, Zhejiang, Peoples R China
来源：
INTERNATIONAL JOURNAL OF HUMAN GENETICS | 2021年 / 21卷 / 02期
关键词：
Epithelial-mesenchymal Transition; MicroRNA-34a; Olaparib; Poly-ADP-ribose Polymerase 1; Sirtuin; 1; EPIDEMIOLOGY; GEMCITABINE; SIRT1;
D O I：
10.3109/24566330.2021/21.02.775
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
This study analyzed functions of miR-34a and SIRT1 in modulating efficacy of Olaparib in pancreatic cancer in vitro. RNA expressions of miR-34a and SIRT1 were evaluated through RT-qPCR in HPDE6-C7, SW1990, PANC-1 and MIA PaCa-2 cells. MiR-34a was promoted in cancer cell lines while SIRT1 was decreased. Luciferase reporter assay verified bindings between miR-34a and SIRT1. Moreover, E-cadherin was promoted by miR-34a mimics and SIRT1 suppression while N-cadherin and Vimentin were both downregulated. Additionally, PARP1 protein expression was increased after miR-34a promotion and SIRT1 downregulation. Besides that, PARP1 protein levels and EMT were significantly inhibited after treated by Olaparib (0, 0.5, 1 and 1.5 mu M). In Olaparib-treated cancer cells, SIRT1, PARP1 and EMT were all distinctly decreased after SIRT1 suppression and overexpression of miR-34a induced much lower level of SIRT1.
引用
收藏
页码：61 / 69
页数：9
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