Zhu Feng, Li Huiyuan, Liu Hongzhang, Wang Yusheng
General Surgery Department of Jincheng People's Hospital, Shanxi, China.
General Surgery Department of Jincheng Hospital Affiliated to Changzhi Medical College, Shanxi, China.
Front Oncol. 2025 Jun 5;15:1582728. doi: 10.3389/fonc.2025.1582728. eCollection 2025.
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.
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).
GPD1L downregulation represents a hallmark of CRC progression, with affecting the expression of HIF-1α and MMP9 significantly impeding malignant behaviors, nominating it as a candidate tumor suppressor in colorectal neoplasia.
阐明代谢相关基因GPD1L在结直肠癌发生过程中的表达谱及肿瘤抑制功能。方法：对来自TCGA和GEO数据库（GSE74602、GSE113513、GSE164191）的转录组数据集进行计算分析。对晋城人民医院58例结直肠癌患者的配对肿瘤/邻近黏膜标本，以及NCM460结肠上皮细胞系和5种结直肠癌细胞系（SW620、HCT116、SW480、DLD-1、LOVO）进行分析。通过qPCR对GPD1L进行定量后，对选定的细胞模型进行pcDNA3.1-GPD1L转染以进行功能表征。然后采用蛋白质印迹分析来探究其可能的机制。
比较分析显示，相对于肿瘤标本，非肿瘤组织中GPD1L的表达显著升高（P<0.001）。转录谱分析进一步确定，与NCM460上皮参照相比，恶性细胞系中GPD1L mRNA水平显著降低（P<0.05），其中HCT116/SW620下调最为明显。异位表达GPD1L可减弱致癌表型：增殖减少（P<0.001），而Transwell定量分析显示迁移能力分别降低46.0%（HCT116：605.0±9.2对326.7±8.50个细胞/视野）和54.3%（SW620：455.3±17.2对208.0±14.0个细胞/视野）（均P<0.001）。侵袭实验显示有类似的抑制作用（HCT116：降低43.3%，P<0.01；SW620：降低54.8% , P<0.001）。GPD1L过表达后，HIF-1α和MMP9的表达水平降低（P<0.05）。
GPD1L下调是结直肠癌进展的一个标志，其通过影响HIF-1α和MMP9的表达显著阻碍恶性行为，表明它是结直肠癌中的一个候选肿瘤抑制因子。
