Ras and Rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancer

Abstract RIN3, a member of the RIN protein family, plays a pivotal role in disease progression by modulating Rab5 activity and influencing cell signaling pathways, which in turn affect tumor proliferation and migration. Our study systematically examined RIN3 expression in various tumor types using d...

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Main Authors: Xin Xu, Ningfeng Zhou, Shasha Zhang, Tingxin Cheng, Jun Ren, Dian Yang, Ying Liu, Shiyan Wang, Aijun Sun, Fengze Cai
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-16067-5
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author Xin Xu
Ningfeng Zhou
Shasha Zhang
Tingxin Cheng
Jun Ren
Dian Yang
Ying Liu
Shiyan Wang
Aijun Sun
Fengze Cai
author_facet Xin Xu
Ningfeng Zhou
Shasha Zhang
Tingxin Cheng
Jun Ren
Dian Yang
Ying Liu
Shiyan Wang
Aijun Sun
Fengze Cai
author_sort Xin Xu
collection DOAJ
description Abstract RIN3, a member of the RIN protein family, plays a pivotal role in disease progression by modulating Rab5 activity and influencing cell signaling pathways, which in turn affect tumor proliferation and migration. Our study systematically examined RIN3 expression in various tumor types using data from TCGA, GTEx, and single-cell RNA sequencing of 77 tumor types in the TISCH database, aiming to clarify its potential role in cancer. We evaluated the association between RIN3 levels and patient survival via univariate Cox regression and analyzed its correlation with immune cell infiltration using TIMER2.0. Additionally, GSEA and GSVA were employed to explore the involvement of RIN3 in immune responses and metabolic processes, while molecular docking and bioinformatics approaches predicted its interactions with anticancer drugs. Functional assays in breast cancer models confirmed that downregulation of RIN3 significantly inhibited cell proliferation and migration. Our results revealed considerable variations in RIN3 expression across tumors, an inverse relationship with CNVs and DNA methylation, and a significant correlation with immunotherapy biomarkers. These findings suggest RIN3 as a promising biomarker and therapeutic target, particularly for BRCA-mutated cancers, and may guide the development of novel anticancer strategies.
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issn 2045-2322
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spelling doaj-art-34e4b02d7aa24aa29b8a0cf68b73a6922025-08-24T11:22:12ZengNature PortfolioScientific Reports2045-23222025-08-0115111510.1038/s41598-025-16067-5Ras and Rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancerXin Xu0Ningfeng Zhou1Shasha Zhang2Tingxin Cheng3Jun Ren4Dian Yang5Ying Liu6Shiyan Wang7Aijun Sun8Fengze Cai9Department of Thyroid and Breast Oncological Surgery, Huai’an Second People’s Hospital, The Affiliated Huaian Hospital of Xuzhou Medical UniversityDepartment of Spinal Surgery, Shanghai East Hospital, School of Medicine, Tongji UniversityKey Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversityFaculty of Life Science and Food Engineering, Huaiyin Institute of TechnologyFaculty of Life Science and Food Engineering, Huaiyin Institute of TechnologyFaculty of Life Science and Food Engineering, Huaiyin Institute of TechnologyFaculty of Life Science and Food Engineering, Huaiyin Institute of TechnologyFaculty of Life Science and Food Engineering, Huaiyin Institute of TechnologyDepartment of Thyroid and Breast Oncological Surgery, Huai’an Second People’s Hospital, The Affiliated Huaian Hospital of Xuzhou Medical UniversityFaculty of Life Science and Food Engineering, Huaiyin Institute of TechnologyAbstract RIN3, a member of the RIN protein family, plays a pivotal role in disease progression by modulating Rab5 activity and influencing cell signaling pathways, which in turn affect tumor proliferation and migration. Our study systematically examined RIN3 expression in various tumor types using data from TCGA, GTEx, and single-cell RNA sequencing of 77 tumor types in the TISCH database, aiming to clarify its potential role in cancer. We evaluated the association between RIN3 levels and patient survival via univariate Cox regression and analyzed its correlation with immune cell infiltration using TIMER2.0. Additionally, GSEA and GSVA were employed to explore the involvement of RIN3 in immune responses and metabolic processes, while molecular docking and bioinformatics approaches predicted its interactions with anticancer drugs. Functional assays in breast cancer models confirmed that downregulation of RIN3 significantly inhibited cell proliferation and migration. Our results revealed considerable variations in RIN3 expression across tumors, an inverse relationship with CNVs and DNA methylation, and a significant correlation with immunotherapy biomarkers. These findings suggest RIN3 as a promising biomarker and therapeutic target, particularly for BRCA-mutated cancers, and may guide the development of novel anticancer strategies.https://doi.org/10.1038/s41598-025-16067-5RIN3Tumor immunityPan-cancerPrognostic biomarkerImmunotherapy
spellingShingle Xin Xu
Ningfeng Zhou
Shasha Zhang
Tingxin Cheng
Jun Ren
Dian Yang
Ying Liu
Shiyan Wang
Aijun Sun
Fengze Cai
Ras and Rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancer
Scientific Reports
RIN3
Tumor immunity
Pan-cancer
Prognostic biomarker
Immunotherapy
title Ras and Rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancer
title_full Ras and Rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancer
title_fullStr Ras and Rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancer
title_full_unstemmed Ras and Rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancer
title_short Ras and Rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancer
title_sort ras and rab interactor 3 as a prognostic biomarker and its impact on immune cell infiltration in cancer
topic RIN3
Tumor immunity
Pan-cancer
Prognostic biomarker
Immunotherapy
url https://doi.org/10.1038/s41598-025-16067-5
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