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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1561210
Identification and Functional Characterization of Prognosis-Related Ferroptosis-Associated lncRNAs in Colorectal Cancer
Provisionally accepted- Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Background: Colorectal cancer (CRC) is a significant global health burden, with current treatment strategies often limited by the TNM classification system's inability to fully capture tumor heterogeneity. This study aims to explore the biological functions and prognostic value of differentially expressed ferroptosis-related long non-coding RNAs (DEFRlncRNAs) in CRC.Methods: We utilized the TCGA database to identify DEFRlncRNAs associated with CRC prognosis. Through multivariate Cox regression analysis, we constructed a prognostic model and selected three key lncRNAs: Lnc-SH2D3A-2, Lnc-LSS-1, and Lnc-PEX11G-4. We assessed their expression in CRC and normal colonic epithelial cell lines using qPCR. Further functional assays included ferroptosis induction with RSL3 and Erastin, cell viability assessments, immunofluorescence staining for lipid peroxidation, and Western blot analysis of ferroptosis-related proteins.Results: Our analysis identified 15 DEFRlncRNAs significantly associated with CRC prognosis, with Lnc-SH2D3A-2, Lnc-LSS-1, and Lnc-PEX11G-4 showing high basal expression in CRC cell lines. Knockdown of Lnc-LSS-1 and Lnc-PEX11G-4 in HT29 and DLD1 cells resulted in significant inhibition of ferroptosis induced by RSL3 and Erastin. The mechanism behind the suppression of ferroptosis by knockdown of Lnc-LSS-1 and Lnc-PEX11G-4 may involve the inhibition of lipid peroxidation and the upregulation of GPX4 expression.Conclusion: DEFRlncRNAs, particularly Lnc-LSS-1 and Lnc-PEX11G-4, play crucial roles in regulating ferroptosis in CRC. These lncRNAs have potential as novel prognostic markers and therapeutic targets, providing valuable insights for personalized CRC treatment strategies.
Keywords: colorectal cancer, ferroptosis, lncRNAs, Prognostic model, therapeutic targets
Received: 15 Jan 2025; Accepted: 03 Apr 2025.
Copyright: © 2025 Ge, Xu, He, Wang and Qian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jian Wang, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Yucheng Qian, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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