Gastrointestinal Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
School of Life Science, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China.
PLoS One. 2022 Jun 7;17(6):e0269094. doi: 10.1371/journal.pone.0269094. eCollection 2022.
In this study, we analyzed GPC family genes in colorectal cancer (CRC) and the possible mechanism of action of GPC1 in CRC. CRC patient data were extracted from The Cancer Genome Atlas, and the prognostic significance of GPC1 expression and its association with clinicopathological features were identified by Kolmogorov-Smirnov test. CRC patients with high GPC1 expression had poor overall survival compared with patients with low GPC1 expression. In vitro experiments demonstrated that knockdown of GPC1 significantly inhibited the proliferation and migration and promoted cell apoptosis in CRC cell lines. Gene Ontology analysis of differential genes indicated that GPC1 may influence the TGF-β1 signaling pathway. Additional experiments revealed that silencing GPC1 suppressed the levels of TGF-β1 and p-SMAD2 but increased the expression of SMAD2. Taken together, these findings suggest that GPC1 may function as a tumor promoter in CRC cells through promoting TGF-β signaling pathway. Our results also indicate that GPC1 may serve as a critical effector in CRC progression and a new potential target for CRC therapy.
在这项研究中，我们分析了结直肠癌（CRC）中的 GPC 家族基因和 GPC1 在 CRC 中的可能作用机制。从癌症基因组图谱中提取 CRC 患者数据，通过 Kolmogorov-Smirnov 检验确定 GPC1 表达的预后意义及其与临床病理特征的关联。与 GPC1 低表达的患者相比，GPC1 高表达的 CRC 患者总生存期较差。体外实验表明，敲低 GPC1 显著抑制 CRC 细胞系的增殖和迁移，并促进细胞凋亡。差异基因的基因本体分析表明，GPC1 可能影响 TGF-β1 信号通路。进一步的实验表明，沉默 GPC1 抑制 TGF-β1 和 p-SMAD2 的水平，而增加 SMAD2 的表达。总之，这些发现表明 GPC1 可能通过促进 TGF-β 信号通路在 CRC 细胞中发挥肿瘤促进作用。我们的结果还表明，GPC1 可能作为 CRC 进展的关键效应物，成为 CRC 治疗的新潜在靶点。
