Mechanism of the RNA Binding Protein ZC3H15 in Mediating the Tumorigenesis of Non-small Cell Lung Cancer
10.11969/j.issn.1673-548X.2025.10.009
- VernacularTitle:RNA结合蛋白ZC3H15介导非小细胞肺癌发生的机制研究
- Author:
Sunan MIAO
1
;
Suhui SHU
1
;
Wei LV
1
Author Information
1. 211166 南京医科大学公共卫生学院流行病学系
- Publication Type:Journal Article
- Keywords:
Copy number variation;
Non-small cell lung cancer;
RNA-binding protein;
ZC3H15;
c-Myc
- From:
Journal of Medical Research
2025;54(10):45-52
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the reasons for the activation of the RNA-binding protein ZC3H15 in non-small cell lung canc-er and its biological functions in the tumorigenesis of non-small cell lung cancer.Methods Based on the whole genome sequencing data of The Cancer Genome Atlas(TCGA)database,the relationship between ZC3H15 copy number variation and its expression was analyzed,and the differential expression of ZC3H15 between normal and non-small cell lung cancer groups,its variation across different TNM sta-ges,and its prognostic analysis were investigated.A549 cells and PC9 cells were divided into si-NC group and si-c-Myc group,re-spectively.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and chromatin immunoprecipitation were used to explore the regulatory relationship between the transcription factor c-Myc and ZC3H15.A549 cells and PC9 cells were divided into si-NC group,si-ZC3H15 1# group,si-ZC3H15 2# group,Vector group,pcDNA-ZC3H15group.RT-qPCR was used to detect the ex-pression of ZC3H15,MTT assay was used to detect cell viability,colony formation assay was used to examine cell proliferation capacity,and Transwell assay was used to measure cell migration ability.The A549 cells were stably transfected with sh-Ctrl and sh-ZC3H15,and the nude mouse xenograft model was used to detect the impact of ZC3H15 on the proliferation ability of non-small cell lung cancer cells in vivo.Results TCGA non-small cell lung cancer data analysis showed that the expression level of ZC3H15 in the copy-number-amplified group was higher than that in the copy-number-deleted group(P＜0.05).ZC3H15 copy number was positively correlated with expression level(P＜0.05).In both paired and unpaired non-small cell lung cancer groups,the expression level of ZC3H15 was up-regulated compared to the normal group(P＜0.05).The expression level of ZC3H15 was higher in stage Ⅲ/Ⅳ group than that in stage Ⅰ/Ⅱ group(P＜0.05).The low-expression ZC3H15group had a higher survival rate than the high-expression group(P＜0.05).Compared to the si-NC group,the expression level of ZC3H15 and Input reference percentage after c-Myc antibody treatment in the si-c-Myc group were both decreased(P＜0.05).The results of RT-qPCR showed that in A549 cells and PC9 cells,the expression level of ZC3H15 in the si-ZC3H15 1# and si-ZC3H15 2# groups were lower than those in the si-NC group(P＜0.05),while the expression level of ZC3H15 in the pcDNA-ZC3H15group was higher than that in the Vector group(P＜0.05).Further cell func-tion studies found that the proliferation and migration capacity of non-small cell lung cancer cells with ZC3H15 knockdown were decreased(P＜0.05),and the overexpression of ZC3H15 could enhance the proliferation and migration capacity of non-small cell lung cancer cells(P＜0.05).At the in vivo level,subcutaneous tumor-bearing experiments in nude mice showed that ZC3H15 knockdown could significant-ly reduced the tumor growth rate(P＜0.05).Conclusion Copy number amplification and c-Myc transcriptional activation were important reasons for ZC3H15 activation in non-small cell lung cancer.ZC3H15 is a key functional molecule to promote the tumorigenesis of non-small cell lung cancer,and can provide some theoretical basis for clinical diagnosis and treatment of non-small cell lung cancer.
