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

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

doi:10.1016/j.jgg.2024.06.002

Volume 51 Issue 10

Oct. 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(10): 1040-1054

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

doi: 10.1016/j.jgg.2024.06.002

a. Laboratory Animal Center, Shanxi Medical University, Taiyuan, Shanxi 030001, China;
b. Department of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi 030001, China;
c. School and Hospital of Stomatology, Shanxi Medical University, Taiyuan, Shanxi 030001, China;
d. Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi 030032, China

Funds:

This work was supported by the National Natural Science Foundation of China (31970513 to G.S.), the Central Government’s Guide to Local Science and Technology Development Fund (YDZJSX2022A060 to G.S.), the special funds for Science and Technology Innovation Teams of Shanxi Province (202204051002032 to G.S.), the Shanxi Province Higher Education “BillionProject” Science and Technology Guidance Project (BYJL016 to G.S.), and the Natural Science Foundation of Shanxi Province (20210302124093 to J.G.).

Received Date: 2024-02-26
Accepted Date: 2024-06-02
Rev Recd Date: 2024-05-29

Available Online: 2025-06-06

Publish Date: 2024-06-11

Abstract

Abstract

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 characteristic 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 activation, 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.
- miR-504,
- CRISPR/Cas9,
- Oral cancer animal model,
- 4NQO,
- Malignant proliferation,
- Lipid metabolism

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References(46)

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