miR-504 knockout regulates tumor cell proliferation and immune cell infiltration to accelerate oral cancer development

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外文摘要：miR-504 plays a pivotal role in the progression of oral cancer.However,the underlying mechanism remains elusive in vivo.Here,we find that miR-504 is significantly down-regulated in oral cancer patients.We generate miR-504 knockout mice(miR-504-/-)using CRISPR/Cas9 technology to investigate its impact on the malignant progression of oral cancer under exposure to 4-Nitroquinoline N-oxide(4NQO).We show that the deletion of miR-504 does not affect phenotypic characteristics,body weight,reproductive performance,and survival in mice,but results in changes in the blood physiological and biochemical indexes of the mice.Moreover,with 4NQO treatment,miR-504-/-mice exhibit more pronounced pathological changes char-acteristic of oral cancer.RNA sequencing shows that the differentially expressed genes observed in samples from miR-504-/-mice with oral cancer are involved in regulating cell metabolism,cytokine acti-vation,and lipid metabolism-related pathways.Additionally,these differentially expressed genes are significantly enriched in lipid metabolism pathways that influence immune cell infiltration within the tumor microenvironment,thereby accelerating tumor development progression.Collectively,our results suggest that knockout of miR-504 accelerates malignant progression in 4NQO-induced oral cancer by regulating tumor cell proliferation and lipid metabolism,affecting immune cell infiltration.

外文关键词：

miR-504CRISPR/Cas9Oral cancer animal model4NQOMalignant proliferationLipid metabolism

作者：

Xiaotang Wang、Xiaona Song、Yunhui Ma、Junting Yang、Jiping Gao、Tian Wang、Guoqiang Xu、Xiaoqi Chang、Shuxuan Shi、Rui Sun、Guohua Song

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作者单位：

Laboratory Animal Center,Shanxi Medical University,Taiyuan,Shanxi 030001,China

Department of Basic Medical Sciences,Shanxi Medical University,Taiyuan,Shanxi 030001,China

School and Hospital of Stomatology,Shanxi Medical University,Taiyuan,Shanxi 030001,China

Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Third Hospital of Shanxi Medical University,Taiyuan,Shanxi 030032,China

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基金：

National Natural Science Foundation of ChinaCentral Government's Guide to Local science and Technology Development Fundspecial funds for Science and Technology Innovation Teams of Shanxi ProvinceShanxi Province Higher Education"BillionProject"Science and Technology Guidance ProjectNatural Science Foundation of Shanxi Province

项目编号：

31970513YDZJSX2022A060202204051002032BYJL01620210302124093

出版年：

2024

DOI：

10.1016/j.jgg.2024.06.002

遗传学报

中国遗传学会中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD

影响因子：0.821

ISSN：1673-8527

年,卷(期)：2024.51(10)