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目的 探究机械离子通道蛋白Piezo1和Yes相关转录蛋白1（Yes-associated transcription protein 1, YAP1）在肝细胞癌（liver hepatocellular carcinoma, LIHC）发生和发展中的作用。方法 使用肿瘤免疫分析数据库（Tumor Immune Estimation Resource, TIMER）和UALCAN数据库分析Piezo1和YAP1在LIHC中的表达水平，以及二者与肿瘤分级、分期、淋巴结转移程度、甲基化水平和患者预后的关系。利用基因表达互作分析（Gene Expression Profiling Interactive Analysis, GEPIA）数据库分析Piezo1和YAP1蛋白表达水平的相关程度及其在不同类型肝癌中的表达水平。利用GeneMANIA数据库分析Piezo1和YAP1的基因互作关系。利用小干扰RNA（small interfering RNA, si-RNA）技术敲低肝癌细胞MHCC97H和Hep3B中的Piezo1，使用实时荧光定量PCR和蛋白质印迹法检测Piezo1、YAP1与核因子κB（nuclear factor κB, NF-κB）通路相关蛋白和细胞外基质（extracellular matrix, ECM）相关蛋白的表达水平。通过Cell Counting Kit-8（CCK-8）实验、transwell实验和平板克隆实验探究敲低Piezo1对细胞增殖和侵袭能力的影响。结果 TIMER、UALCAN和GEPIA数据库分析显示，Piezo1和YAP1均在LIHC中协同高表达，且其表达与LIHC分级、分期、淋巴结转移程度和DNA启动子甲基化相关，差异均具有统计学意义（均P < 0.05），并降低LIHC患者的预后。GeneMANIA数据库分析显示，Piezo1和YAP1形成丰富的基因通讯网络，共同促进肿瘤相关成纤维细胞的浸润。PCR结果显示，Piezo1和YAP1在肝癌细胞系MHCC97H、Hep3B和HepG2中均高表达（均P < 0.05）。敲低MHCC97H细胞中的Piezo1后，YAP1的表达水平降低，NF-κB信号通路的磷酸化的核因子κB抑制蛋白α（phospho-nuclear factor κB inhibitor alpha, p-IKB-α）和p-NF-κB被抑制，ECM相关蛋白fibronectin和collagen Ⅰ的表达亦下调；同时，细胞增殖、侵袭和克隆形成能力均被抑制（均P < 0.05）。结论 Piezo1和YAP1在LIHC中协同高表达。Piezo1通过调控YAP1增强LIHC的增殖和侵袭能力，二者重塑肿瘤微环境，促进肝癌的恶性进展，降低患者的预后。
Abstract：Objective To investigate the roles of the mechanosensitive ion channel protein Piezo1 and Yes-associated transcription protein 1 (YAP1) in the development of liver hepatocellular carcinoma (LIHC). Methods The expression levels of Piezo1 and YAP1 in LIHC, as well as their relationship with tumor grade, stage, lymph node metastasis, methylation level, and patient prognosis, were analyzed using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. The correlation between Piezo1 and YAP1 protein expression levels and their expressions in different types of liver cancer were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. The gene interaction network between Piezo1 and YAP1 was analyzed using the GeneMANIA database. Small interfering RNA (si-RNA) was used to knock down Piezo1 in liver cancer cells MHCC97H and Hep3B. The expression levels of Piezo1, YAP1, nuclear factor κB (NF-κB) pathway-related proteins, and extracellular matrix (ECM)-related proteins were detected using quantitative real-time PCR and Western blot. Cell proliferation and invasion abilities after Piezo1 knockdown were evaluated using Cell Counting Kit-8 (CCK-8) assay, transwell assay, and colony formation assay. Results The analysis of TIMER, UALCAN, and GEPIA databases showed that both Piezo1 and YAP1 were synergistically highly expressed in LIHC, and their expressions were associated with LIHC grade, stage, lymph node metastasis, and DNA promoter methylation (all P < 0.05), and correlated with poor prognosis in LIHC patients. GeneMANIA database analysis revealed that Piezo1 and YAP1 form an extensive gene interaction network, collectively promoting the infiltration of cancer-associated fibroblasts. PCR results indicated that Piezo1 and YAP1 were highly expressed in liver cancer cell lines MHCC97H, Hep3B, and HepG2 (all P < 0.05). After knocking down Piezo1 in MHCC97H cells, the expression of YAP1 decreased, the phosphorylation of NF-κB inhibitor alpha (IκB-α) and p-NF-κB in the NF-κB signaling pathway was inhibited, and the expressions of ECM-related proteins fibronectin and collagen Ⅰ were reduced. Meanwhile, cell proliferation, invasion, and colony formation abilities were suppressed (all P < 0.05). Conclusions Piezo1 and YAP1 are synergistically highly expressed in LIHC. Piezo1 enhances the proliferation and invasion abilities of LIHC by regulating YAP1, reshaping tumor microenvironment to promote the malignancy of liver cancer and harm patients' prognosis.
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基本信息:
DOI：10.13267/j.cnki.syzlzz.2026.006
引用信息:
[1]王桁扬,丁敬健,王涛,等.Piezo1通过YAP1促进肝细胞癌发生和发展[J],2026,41(1):33-43.DOI:10.13267/j.cnki.syzlzz.2026.006.