Luo Xianwei, Gao Zhenming
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, China.
Protein Pept Lett. 2025;32(3):224-233. doi: 10.2174/0109298665359781250114055525.
MARVEL domain-containing 1 (MARVELD1) has been implicated in the progression of several cancers, but its role in pancreatic adenocarcinoma (PAAD) remains poorly understood.
RNA-seq data from the TCGA-PAAD and GTEx-Pancreas cohorts were analyzed to assess MARVELD1 expression. Stable MARVELD1 knockdown and overexpression were conducted in BxPC3 and PANC-1 cells. Cell viability, proliferation, migration, and invasion were evaluated using functional assays, and western blotting was employed to examine EMT-associated protein levels, including Vimentin, MMP2, MMP9, and E-cadherin. Differentially expressed genes (DEGs) between MARVELD1-high and MARVELD1-low groups were identified, and pathway enrichment analyses were performed.
We observed a significant increase of MARVELD1 in PAAD patient samples, with elevated MARVELD1 levels correlating with poor clinical survival. Knockdown of MARVELD1 in PAAD cells remarkably decreased cell proliferation and colony formation, while overexpression of MARVELD1 enhanced these properties. Moreover, simulated cell invasion and migration assay further suggested that MARVELD1 might contribute to PAAD cell aggressiveness. Mechanistically, MARVELD1 promoted tumor cell migration and invasion through the activation of Vimentin, MMP2, and MMP9 protein while suppressing E-cadherin. Bioinformatics analysis revealed that MARVELD1-high samples were enriched in EMT-related pathways, including TGF-β receptor signaling, actin cytoskeleton regulation, and cell adhesion.
Taken together, our study highlights the roles of MARVELD1 in promoting tumor cell proliferation and invasion, suggesting its potential application as a prognostic and diagnostic biomarker for PAAD in the clinical context.
含MARVEL结构域蛋白1（MARVELD1）与多种癌症的进展有关，但其在胰腺腺癌（PAAD）中的作用仍知之甚少。
分析来自TCGA-PAAD和GTEx-胰腺队列的RNA测序数据，以评估MARVELD1的表达。在BxPC3和PANC-1细胞中进行MARVELD1的稳定敲低和过表达。使用功能测定评估细胞活力、增殖、迁移和侵袭，并采用蛋白质免疫印迹法检测与上皮-间质转化（EMT）相关的蛋白水平，包括波形蛋白、基质金属蛋白酶2（MMP2）、基质金属蛋白酶9（MMP9）和E-钙黏蛋白。鉴定MARVELD1高表达组和低表达组之间的差异表达基因（DEG），并进行通路富集分析。
我们观察到PAAD患者样本中MARVELD1显著增加，MARVELD1水平升高与临床生存率低相关。在PAAD细胞中敲低MARVELD1可显著降低细胞增殖和集落形成，而MARVELD1过表达则增强了这些特性。此外，模拟细胞侵袭和迁移试验进一步表明，MARVELD1可能促进PAAD细胞的侵袭性。机制上，MARVELD1通过激活波形蛋白、MMP2和MMP9蛋白，同时抑制E-钙黏蛋白，促进肿瘤细胞迁移和侵袭。生物信息学分析显示，MARVELD1高表达样本富集于与EMT相关的通路，包括转化生长因子-β（TGF-β）受体信号传导、肌动蛋白细胞骨架调节和细胞黏附。
综上所述，我们的研究突出了MARVELD1在促进肿瘤细胞增殖和侵袭中的作用，表明其在临床环境中作为PAAD预后和诊断生物标志物的潜在应用价值。
