MTHFD2 Is a Negative Regulatory Molecule for the Formation of Heterotypic Cell-in-Cell Structures
10.13865/j.cnki.cjbmb.2024.03.1057
- VernacularTitle:亚甲基四氢叶酸脱氢酶2是异质性细胞叠套结构形成的负调控分子
- Author:
Peng-Fei FENG
1
,
2
,
3
;
Chen-Yu LIU
;
Yi-Nuo HUANG
;
Zhuo-Ran SUN
;
Yang-Yi ZHANG
;
Hong-Yan HUANG
;
Chen-Xi WANG
;
Xiao-Ning WANG
Author Information
1. 解放军医学院研究生院,北京 100853
2. 解放军总医院第二医学中心老年医学研究所衰老与相关疾病研究北京市重点实验室国家老年疾病临床医学研究中心,北京 100853
3. 军事医学研究院生物工程研究所,北京 100071
- Keywords:
methylenetetrahydrofolata dehydrogenase 2(MTHFD2);
heterotypic cell-in-cell structure(heCICs);
liver cancer;
immunotherapy
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(6):819-826
- CountryChina
- Language:Chinese
-
Abstract:
Heterotypic cell-in-cell structures(heCICs)mediate unique non-autonomous cell death,which are widely involved in a variety of important pathological processes,such as tumorigenesis,pro-gression and clinical prognosis.Methylenetetrahydrofolata dehydrogenase 2(MTHFD2),one of the key enzymes of one-carbon metabolism,is highly expressed in a variety of tumor cells.In this study,in order to investigate the effect of MTHFD2 on the formation of heCICs,liver cancer cells and immune cells were first labeled separately by live cell dyes,and the heCIC model was established by using fluorescence mi-croscopy for cell imaging and analysis.After transiently knocking down MTHFD2 in cells by RNAi,we found that the ability of PLC/PRF/5 and Hep3B to form heCICs with immune cells was significantly in-creased(all P＜0.01).MTHFD2 recombinant expression plasmid was constructed by the homologous re-combination method,and MTHFD2 overexpression cell lines were further constructed.Then,the effect of MTHFD2 overexpression on the ability to form heCICs was detected by co-culturing the overexpression cell lines with immune cells.The results showed that the rate of heCIC formation was significantly re-duced after overexpression of MTHFD2(all P＜0.001).In conclusion,this study demonstrated that MTHFD2 is a negative regulator of heCIC formation,providing a research basis for targeting MTHFD2 to promote heCIC formation and enhance the in-cell killing of immune cells.
