IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma
Abstract ABCA1 is a key protein in maintaining cholesterol homeostasis, and its abnormal expression is associated with the progression of many cancers. Nonetheless, the specific molecular mechanisms by which ABCA1 facilitates the development of LUAD remain largely unexplored, necessitating further i...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-08-01
|
| Series: | Amino Acids |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s00726-025-03474-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849226148961058816 |
|---|---|
| author | Shaohua Xu Kai Liu Zhao Chen Weijian Tang Zhoumiao Chen |
| author_facet | Shaohua Xu Kai Liu Zhao Chen Weijian Tang Zhoumiao Chen |
| author_sort | Shaohua Xu |
| collection | DOAJ |
| description | Abstract ABCA1 is a key protein in maintaining cholesterol homeostasis, and its abnormal expression is associated with the progression of many cancers. Nonetheless, the specific molecular mechanisms by which ABCA1 facilitates the development of LUAD remain largely unexplored, necessitating further in-depth investigation. The TCGA-LUAD database was used to analyze the expression of ABCA1 in LUAD tissues. Subsequently, a cell model with overexpressed ABCA1 was constructed for verification through cell experiments. Cell function was evaluated using the Transwell assay and the colony formation assay. Intracellular cholesterol levels were detected using a kit. At the same time, the online database RM2 Target was employed to predict upstream factors that may have a methylation regulatory relationship with ABCA1. On this basis, Dot blot and MeRIP-qPCR techniques were employed to determine the degree of m6A modification. To clarify the mechanism of IGF2BP1 regulating ABCA1 through the m6A pathway, RNA pull-down binding experiments were carried out, and changes in mRNA stability were assessed using actinomycin D treatment. Finally, the biological function of the IGF2BP1/ABCA1 signaling axis during the growth and metastasis of LUAD in vivo was evaluated by establishing a xenograft animal model. Bioinformatics analysis and cell experimental results confirmed the low expression of ABCA1 in LUAD tissues and cells. ABCA1 significantly inhibited cell proliferation, migration, and invasion capabilities, promoted apoptosis, and reduced intracellular cholesterol levels. From a molecular perspective, IGF2BP1 recognized and bound to methylation sites on ABCA1 mRNA, thereby accelerating its degradation process, resulting in a substantial decrease in the stability of ABCA1 mRNA. Moreover, in vivo and in vitro experiments further confirmed that IGF2BP1 affected cholesterol metabolism by regulating the expression of ABCA1, thereby facilitating the malignant progression of LUAD. Overall, our research revealed that IGF2BP1 affects cholesterol metabolism by reducing the stability of ABCA1 mRNA through m6A modification, thereby boosting the malignant progression of LUAD and formulating a theoretical basis for subsequent LUAD treatment. |
| format | Article |
| id | doaj-art-9822352b07f340fda34c6dad41a158b8 |
| institution | Kabale University |
| issn | 1438-2199 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Amino Acids |
| spelling | doaj-art-9822352b07f340fda34c6dad41a158b82025-08-24T11:35:57ZengSpringerAmino Acids1438-21992025-08-0157111410.1007/s00726-025-03474-1IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinomaShaohua Xu0Kai Liu1Zhao Chen2Weijian Tang3Zhoumiao Chen4Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAbstract ABCA1 is a key protein in maintaining cholesterol homeostasis, and its abnormal expression is associated with the progression of many cancers. Nonetheless, the specific molecular mechanisms by which ABCA1 facilitates the development of LUAD remain largely unexplored, necessitating further in-depth investigation. The TCGA-LUAD database was used to analyze the expression of ABCA1 in LUAD tissues. Subsequently, a cell model with overexpressed ABCA1 was constructed for verification through cell experiments. Cell function was evaluated using the Transwell assay and the colony formation assay. Intracellular cholesterol levels were detected using a kit. At the same time, the online database RM2 Target was employed to predict upstream factors that may have a methylation regulatory relationship with ABCA1. On this basis, Dot blot and MeRIP-qPCR techniques were employed to determine the degree of m6A modification. To clarify the mechanism of IGF2BP1 regulating ABCA1 through the m6A pathway, RNA pull-down binding experiments were carried out, and changes in mRNA stability were assessed using actinomycin D treatment. Finally, the biological function of the IGF2BP1/ABCA1 signaling axis during the growth and metastasis of LUAD in vivo was evaluated by establishing a xenograft animal model. Bioinformatics analysis and cell experimental results confirmed the low expression of ABCA1 in LUAD tissues and cells. ABCA1 significantly inhibited cell proliferation, migration, and invasion capabilities, promoted apoptosis, and reduced intracellular cholesterol levels. From a molecular perspective, IGF2BP1 recognized and bound to methylation sites on ABCA1 mRNA, thereby accelerating its degradation process, resulting in a substantial decrease in the stability of ABCA1 mRNA. Moreover, in vivo and in vitro experiments further confirmed that IGF2BP1 affected cholesterol metabolism by regulating the expression of ABCA1, thereby facilitating the malignant progression of LUAD. Overall, our research revealed that IGF2BP1 affects cholesterol metabolism by reducing the stability of ABCA1 mRNA through m6A modification, thereby boosting the malignant progression of LUAD and formulating a theoretical basis for subsequent LUAD treatment.https://doi.org/10.1007/s00726-025-03474-1IGF2BP1ABCA1m6A methylationCholesterol metabolismLung adenocarcinoma |
| spellingShingle | Shaohua Xu Kai Liu Zhao Chen Weijian Tang Zhoumiao Chen IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma Amino Acids IGF2BP1 ABCA1 m6A methylation Cholesterol metabolism Lung adenocarcinoma |
| title | IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma |
| title_full | IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma |
| title_fullStr | IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma |
| title_full_unstemmed | IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma |
| title_short | IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma |
| title_sort | igf2bp1 mediated methylation of abca1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma |
| topic | IGF2BP1 ABCA1 m6A methylation Cholesterol metabolism Lung adenocarcinoma |
| url | https://doi.org/10.1007/s00726-025-03474-1 |
| work_keys_str_mv | AT shaohuaxu igf2bp1mediatedmethylationofabca1facilitatestumorprogressionbyaffectingcholesterolmetabolisminlungadenocarcinoma AT kailiu igf2bp1mediatedmethylationofabca1facilitatestumorprogressionbyaffectingcholesterolmetabolisminlungadenocarcinoma AT zhaochen igf2bp1mediatedmethylationofabca1facilitatestumorprogressionbyaffectingcholesterolmetabolisminlungadenocarcinoma AT weijiantang igf2bp1mediatedmethylationofabca1facilitatestumorprogressionbyaffectingcholesterolmetabolisminlungadenocarcinoma AT zhoumiaochen igf2bp1mediatedmethylationofabca1facilitatestumorprogressionbyaffectingcholesterolmetabolisminlungadenocarcinoma |