PORCN promotes hepatocellular carcinogenesis via Wnt/β-catenin-dependent manner.
PORCN promotes hepatocellular carcinogenesis via Wnt/β-catenin-dependent manner.
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DOI：
10.21037/tcr-23-191
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发表时间：
2023-07-31
影响因子：
0.9
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中科院分区：
文献类型：
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豪猪 O-酰基转移酶 (PORCN) 是一种膜结合的 O-酰基转移酶，在 Wnt 配体棕榈酰化中至关重要。然而，PORCN 在肝细胞癌 (HCC) 发展中的作用仍不清楚。使用蛋白质印迹、实时定量聚合酶链反应 (RT-qPCR) 检测和癌症基因组图谱 (TCGA) 数据库来研究 HCC 患者中 PORCN 的表达和预后价值。随后，采用细胞计数试剂盒-8 (CCK-8)、伤口愈合测试、Transwell 实验和异种移植小鼠模型来检查 PORCN 对 HCC 细胞的影响。最后，确定了 PORCN 引起的细胞增殖和迁移的潜在分子机制。 HCC组织中PORCN的蛋白和信使RNA（mRNA）水平高于癌旁正常组织。 TCGA数据库分析表明，PORCN表达较高的患者总生存率较低。 PORCN的过表达可以促进HCC细胞的体外和体内增殖和迁移能力。基因集富集分析（GSEA）显示，PORCN对HCC细胞生物学特性的影响主要集中在Wnt-β-catenin信号通路上。机械方面，免疫荧光染色和亚细胞蛋白组分分析表明，PORCN 可以通过促进 β-catenin 从细胞质到细胞核的易位来诱导上皮间质转化（EMT），最终促进 HCC 的进展。本研究结果表明，PORCN可以通过刺激Wnt-β-catenin信号通路促进HCC细胞增殖和迁移。因此，PORCN可能是HCC有前景的治疗靶点。
Porcupine O-acyltransferase (PORCN), a membrane-bound O-acyltransferase, is crucial in Wnt ligand palmitoylation. However, the roles of PORCN in the development of hepatocellular carcinoma (HCC) remain unknown. Western blot, real-time quantitative polymerase chain reaction (RT-qPCR) assays, and The Cancer Genome Atlas (TCGA) database were used to study the expression and prognostic values of PORCN in patients with HCC. Following this, Cell Counting Kit-8 (CCK-8), wound-healing tests, Transwell assay, and a xenograft mouse model were employed to examine the effect of PORCN on HCC cells. Finally, the underlying molecular mechanisms involved in cell proliferation and migration caused by PORCN were identified. The protein and messenger RNA (mRNA) levels of PORCN in HCC tissues were higher than those of adjacent normal tissues. The analysis of TCGA database indicated that patients with higher PORCN expression had a lower overall survival (OS) rate. Overexpression of PORCN could promote the proliferation and migration abilities of HCC cells both in vitro and in vivo. Gene set enrichment analysis (GSEA) showed that the effect of PORCN on the biological characteristics of HCC cells mainly centered on the Wnt-β-catenin signaling pathway. Mechanically, immunofluorescence staining and subcellular protein fraction assays showed that PORCN could induce epithelial-mesenchymal transition (EMT) by promoting the translocation of β-catenin from the cytoplasm to nucleus, ultimately promoting the progression of HCC. The findings of this study suggest that PORCN can promote HCC cell proliferation and migration by stimulating the Wnt-β-catenin signaling pathway. Therefore, PORCN may be a promising therapeutic target for HCC.