IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma
RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show...
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2025-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/14/15/1222 |
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| author | Feiming Hu Chenchen Hu Yuanli He Lin Guo Yuanjie Sun Chenying Han Xiyang Zhang Junyi Ren Jinduo Han Jing Wang Junqi Zhang Yubo Sun Sirui Cai Dongbo Jiang Kun Yang Shuya Yang |
| author_facet | Feiming Hu Chenchen Hu Yuanli He Lin Guo Yuanjie Sun Chenying Han Xiyang Zhang Junyi Ren Jinduo Han Jing Wang Junqi Zhang Yubo Sun Sirui Cai Dongbo Jiang Kun Yang Shuya Yang |
| author_sort | Feiming Hu |
| collection | DOAJ |
| description | RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine. |
| format | Article |
| id | doaj-art-d565b33be8ec4c449fa4dcbf77f0cf4c |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-d565b33be8ec4c449fa4dcbf77f0cf4c2025-08-20T03:02:58ZengMDPI AGCells2073-44092025-08-011415122210.3390/cells14151222IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung AdenocarcinomaFeiming Hu0Chenchen Hu1Yuanli He2Lin Guo3Yuanjie Sun4Chenying Han5Xiyang Zhang6Junyi Ren7Jinduo Han8Jing Wang9Junqi Zhang10Yubo Sun11Sirui Cai12Dongbo Jiang13Kun Yang14Shuya Yang15Department of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaMilitary Medical Innovation Center, Air Force Medical University, Xi’an 710032, ChinaSchool of Basic Medicine, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaSchool of Basic Medicine, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaSchool of Basic Medicine, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaDepartment of Immunology, Air Force Medical University, No. 169, Changle West Road, Xi’an 710032, ChinaRNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine.https://www.mdpi.com/2073-4409/14/15/1222IGF2BP3lung adenocarcinomatherapeutic targettumor immune microenvironmentprognostic biomarker |
| spellingShingle | Feiming Hu Chenchen Hu Yuanli He Lin Guo Yuanjie Sun Chenying Han Xiyang Zhang Junyi Ren Jinduo Han Jing Wang Junqi Zhang Yubo Sun Sirui Cai Dongbo Jiang Kun Yang Shuya Yang IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma Cells IGF2BP3 lung adenocarcinoma therapeutic target tumor immune microenvironment prognostic biomarker |
| title | IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma |
| title_full | IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma |
| title_fullStr | IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma |
| title_full_unstemmed | IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma |
| title_short | IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma |
| title_sort | igf2bp3 as a novel prognostic biomarker and therapeutic target in lung adenocarcinoma |
| topic | IGF2BP3 lung adenocarcinoma therapeutic target tumor immune microenvironment prognostic biomarker |
| url | https://www.mdpi.com/2073-4409/14/15/1222 |
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