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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2025 02

Page:

208-217

Research Field:

Publishing date:

Info

Title:

Effect of exosomal circ-0001328 on gemcitabine resistance in gallbladder cancer cells by targeting miR-545-3p

Author(s):

CHEN Ping¹; WU Jianchun¹; YANG Zhen²; JIANG Shihao²; ZHOU Ning²

1.Department of General Surgery,the First People’s Hospital of Changsha County,Hunan Changsha 410142,China;2.Department of Hepatobiliary Surgery,Hunan Provincial People’s Hospital,the First Affiliated Hospital of Hunan Normal University,Hunan Changsha 410011,China.

Keywords:

circ-0001328; miR-545-3p; gallbladder cancer cells; GEM resistance; glutamine metabolism

PACS:

R735.8

DOI:

10.3969/j.issn.1672-4992.2025.02.007

Abstract:

Objective:To investigate the effect of circ-0001328 and miR-545-3p on gemcitabine (GEM) resistance in gallbladder cancer cells and to explore the related mechanism.Methods:Exosomes were extracted from gallbladder cancer cells (NOZ,GBC-SD and SGC-996) and GEM-resistant gallbladder cancer cells (NOZ/G,GBC-SD/G and SGC-996/G),and the expression levels of circ-0001328 and miR-545-3p were detected by qRT-PCR.NOZ/G cells were transfected with sh-NC vector (sh-NC group),sh-circ-0001328 vector (sh-circ-0001328 group),inhibitor-NC (inhibitor-NC group),miR-545-3p inhibitor (miR-545-3p inhibitor group),sh-circ-0001328+miR-545-3p inhibitor (sh-circ-0001328+miR-545-3p inhibitor group),respectively.The semi-inhibitory concentration (IC50) and optical density (OD) values of GEM were detected by CCK-8,cell proliferation was detected by EdU staining,cell apoptosis rate was detected by flow cytometry,expression levels of proliferation-associated proteins (Cyclin E1 and CDK2) and apoptosis-associated proteins (Caspase-3 and Bax) were detected by Western blot,and glutamine metabolism including glutamine (Gln) uptake and glutamate (Glu) and α-ketoglutarate (α-KG) production were detected by related kits.The regulatory relationship between circ-0001328 and miR-545-3p was validated by bioinformatics analysis,luciferase reporter gene and RIP assays.Results:Compared with gallbladder cancer cells,circ-0001328 expression was upregulated and miR-545-3p expression was downregulated in the exosomes of GEM-resistant gallbladder cancer cells,with NOZ/G cells showing the most significant expression (P＜0.05).Compared with the sh-NC group,the IC50,24,48,72 h OD values were decreased,EdU positive rate,Cyclin E1 and CDK2 proteins expression were decreased,apoptosis rate,Caspase-3 and Bax proteins expression were increased,and Gln uptake,Glu and α-KG production were reduced in the sh-circ-0001328 group (P＜0.05).Compared with the inhibitor-NC group,the IC50,24,48,72 h OD values were increased,EdU positive rate,Cyclin E1 and CDK2 protein expression were increased,apoptosis rate,Caspase-3 and Bax protein expression were decreased,and Gln uptake,Glu and α-KG production were increased in the miR-545-3p inhibitor group (P＜0.05).Compared with the sh-circ-0001328 group,the IC50,24,48,72 h OD values were increased,EdU positive rate,Cyclin E1 and CDK2 protein expression were increased,apoptosis rate,Caspase-3 and Bax protein expression were decreased,and Gln uptake,Glu and α-KG production were increased in the sh-circ-0001328+miR-545-3p inhibitor group (P＜0.05).miR-545-3p was a target gene of circ-0001328,and circ-0001328 directly inhibited miR-545-3p expression.Conclusion:circ-0001328 expression is upregulated and miR-545-3p expression is downregulated in the exosomes of GEM-resistant gallbladder cells.circ-0001328 enhances GEM resistance in gallbladder cells by targeting miR-545-3p,and the mechanism may be related to the promotion of glutamine metabolism.

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Memo

Memo:

湖南省自然科学基金科卫联合项目（编号：2022JJ70100）；湖南省临床医疗技术创新引导项目(编号：2021SK50913)

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