ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1582728
GPD1L Downregulation in Colorectal Cancer: A Novel Obesity-Related Biomarker Linking Metabolic Dysregulation to Tumor Progression
Provisionally accepted
- Jincheng People's Hospital, Jincheng City, China
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Objective: To delineate the expression profile and tumor-suppressive function of the metabolism-associated gene GPD1L in colorectal carcinogenesis. Methods: Transcriptomic datasets from TCGA and GEO repositories (GSE74602, GSE113513, GSE164191) were computationally analyzed. Paired tumor/adjacent mucosal specimens (n=58) from CRC patients at Jincheng People's Hospital were analyzed alongside the NCM460 colon epithelial line and five CRC lines (SW620, HCT116, SW480, DLD-1, LOVO). Following GPD1L quantification via qPCR, selected cell models underwent pcDNA3.1-GPD1L transfection for functional characterization.Then Western blot analysis was used to explore its possible mechanism. Results:Comparative analysis revealed a marked elevation of GPD1L expression in non-neoplastic tissues relative to tumor specimens (P<0.001). Transcriptional profiling further identified significant depletion of GPD1L mRNA levels across malignant cell lines versus the NCM460 epithelial reference (P<0.05), with HCT116/SW620 showing maximal downregulation. Ectopic GPD1L expression attenuated oncogenic phenotypes: proliferation decreased(P<0.001), while Transwell quantification revealed 46.0% (HCT116: 605.0±9.2 vs 326.7±8.50 cells/field) and 54.3% (SW620: 455.3±17.2 vs 208.0±14.0 cells/field) reductions in migratory capacity (both P<0.001). Invasion assays showed parallel inhibition (HCT116: 43.3% decrease, P<0.01; SW620: 54.8% decrease, P<0.001). After overexpression of GPD1L, the expression levels of HIF-1α and MMP9 were reduced (P<0.05).affecting the expression of HIF-1α and MMP9 significantly impeding malignant behaviors, nominating it as a candidate tumor suppressor in colorectal neoplasia.
Keywords: Metabolism-Associated Gene, colorectal cancer, GPD1L, bioinformatics, tumor suppressor genes
Received: 24 Feb 2025; Accepted: 22 May 2025.
Copyright: © 2025 Zhu, Li, Liu and Wang. 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:
Hongzhang Liu, Jincheng People's Hospital, Jincheng City, China
Yusheng Wang, Jincheng People's Hospital, Jincheng City, China
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