Peng Peng, Sun Juan, Li Meng-Shi, Cheng Ruo-Xi, Liu Shi-Quan, Qin Meng-Bin, Zhang Jin-Xiu, Huang Jie-An
Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Zhuang Autonomous Region, China.
World J Gastrointest Oncol. 2025 May 15;17(5):104686. doi: 10.4251/wjgo.v17.i5.104686.
In patients with colorectal cancer (CRC), tumour metastasis is the leading cause of death. The search for key genes involved in metastasis of CRC is imperative for improved prognoses and treatments. has been implicated in the development of CRC, however, its mechanism of action remains unclear.
To investigate the role and mechanism of action by which SPDL1 inhibits the development and metastasis of CRC.
In this study, we examined the relationship between SPDL1 expression and CRC prognosis using immunohistochemistry. Survival analyses were performed using Kaplan-Meier analysis and log-rank test. After knocking down SPDL1 in the HCT116 cancer cell line changes in cell viability, migration, invasion, and gene expression were examined using a cell counting kit 8 assay, Transwell assay, and Western blot. The effect of SPDL1 on the cell cycle was assessed using flow cytometry. RNA sequencing was used to analyse the effect of SPDL1 on gene expression of CRC cells. The mechanism of action of SPDL1 in CRC was further clarified using U0126, an inhibitor of the mitogen-activated protein kinase signaling pathway.
SPDL1 is expressed at low levels in tissues of patients with CRC, and this reduced expression is associated with poor prognosis. Functionally, low expression of SPDL1 in CRC promotes cell proliferation, migration, invasion, and affects the cell cycle. Mechanistically, SPDL1 affects the progression of CRC through its regulation of the process of epithelial-mesenchymal transition (EMT) and of the epidermal growth factor receptor (EGFR)/ extracellular signal-regulated kinase (ERK) signaling pathways.
This study showed that the loss of SPDL1 may induce EMT and promote cell migration and invasion in CRC through the EGFR/ERK pathway.
在结直肠癌（CRC）患者中，肿瘤转移是主要的死亡原因。寻找参与CRC转移的关键基因对于改善预后和治疗至关重要。 已被认为与CRC的发生发展有关，然而，其作用机制仍不清楚。
研究SPDL1抑制CRC发生发展和转移的作用及机制。
在本研究中，我们使用免疫组织化学检查SPDL1表达与CRC预后之间的关系。使用Kaplan-Meier分析和对数秩检验进行生存分析。在HCT116癌细胞系中敲低SPDL1后，使用细胞计数试剂盒8检测、Transwell检测和蛋白质印迹法检测细胞活力、迁移、侵袭和基因表达的变化。使用流式细胞术评估SPDL1对细胞周期的影响。RNA测序用于分析SPDL1对CRC细胞基因表达的影响。使用丝裂原活化蛋白激酶信号通路抑制剂U0126进一步阐明SPDL1在CRC中的作用机制。
SPDL1在CRC患者组织中低表达，这种低表达与预后不良相关。在功能上，CRC中SPDL1的低表达促进细胞增殖、迁移、侵袭，并影响细胞周期。在机制上，SPDL1通过调节上皮-间质转化（EMT）过程和表皮生长因子受体（EGFR）/细胞外信号调节激酶（ERK）信号通路来影响CRC的进展。
本研究表明，SPDL1的缺失可能通过EGFR/ERK途径诱导EMT并促进CRC中的细胞迁移和侵袭。
