DSCR9/miR-21-5p axis inhibits pancreatic cancer proliferation and resistance to gemcitabine via BTG2 signaling  

作　　者：Hui Huang Xia Li Xianlin Zhang Zhiqiang Li Duo Han Wenzhe Gao Ling Liu Cheng Peng Hongwei Zhu Xiao Yu 

机构地区：[1]Department of Hepatopancreatobiliary Surgery,Third Xiangya Hospital,Central South University,Changsha 410013,China [2]Department of Endocrinology,Third Xiangya Hospital,Central South University,Changsha 410013,China [3]Department of General Surgery,Affiliated Renhe Hospital of China Three Gorges University,Yichang 443001,China [4]Department of Cardiology,Second People’s Hospital of Hunan Province,Hunan University of Chinese Medicine,Changsha 410007,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第12期1775-1788,共14页生物化学与生物物理学报（英文版）

基　　金：supported by the grant from the National Natural Science Foundation of China(No.81873589).

摘　　要：The outcome of pancreatic adenocarcinoma(PAAD)patients is poor,given resistance to gemcitabine.Long noncoding RNA(lncRNA)has been implicated in the carcinogenesis of pancreatic cancer;however,its function and mechanism in PAAD resistance to gemcitabine(GEM)are yet unknown.Herein,we demonstrate that lncRNA DSCR9 is significantly reduced in PAAD in vitro and in vivo.CCK-8,BrdU and flow cytometry assays show that overexpression of DSCR9 markedly suppresses pancreatic cancer cell proliferation and invasion,and promotes apoptosis under gemcitabine treatment.BTG2 acts as a tumor suppressor by reducing the proliferation and invasion of pancreatic cancer cells and increasing gemcitabine-induced apoptosis.Immunofluorescence(IF)staining combined with fluorescence in situ hybridization(FISH)of pancreatic cancer tissues shows that DSCR9 and BTG2 are both increased in pancreatic cancer tissues.Luciferase assay shows that miR-21-5p simultaneously binds to DSCR9 and 3′UTR of BTG2;DSCR9 relieves miR-21-5p-induced inhibition of BTG2 by competing with BTG2 for miR-21-5p binding.Overexpression of miR-21-5p enhances the invasiveness of pancreatic cancer cells by promoting cancer cell proliferation and invasion and attenuating gemcitabine-induced apoptosis.Overexpression of miR-21-5p attenuates the effect of DSCR9 overexpression on BTG2 expression and invasiveness of pancreatic cancer cells.Finally,miR-21-5p expression is increased,while BTG2 expression is decreased in pancreatic cancer tissues.miR-21-5p is negatively correlated with DSCR9 and BTG2.In conclusion,the DSCR9/miR-21-5p/BTG2 axis modulates pancreatic cancer proliferation,invasion,and gemcitabine resistance.

关 键 词：pancreatic cancer lncRNA DSCR9 miR-21-5p BTG2 PROLIFERATION gemcitabine resistance 

分 类 号：R735.9[医药卫生—肿瘤]