Tumor Diagnosis and Treatment Center of Kaifeng Central Hospital, Kaifeng, 475001 Henan, China.
Analysis Department, Central Hospital of Kaifeng, Kaifeng, 475001 Henan, China.
Biomed Res Int. 2020 Dec 9;2020:7467104. doi: 10.1155/2020/7467104. eCollection 2020.
Gastric carcinoma is a common malignant cancer. Pyruvate kinase M2 (PKM2) is highly expressed in cancers, including gastric carcinoma. However, its function and molecular mechanism in gastric carcinoma remains unclear. Here, we aimed to explore the function and the underlying mechanism of PKM2 on malignant phenotypes in gastric carcinoma. In this study, the mRNA levels and protein levels of PKM2 in gastric carcinoma cell lines and normal gastric mucosa epithelial cell lines were detected using quantitative real-time PCR and western blot, respectively. PKM2 was downregulated by siRNA transfection. HIF-1 or BCL-6 was upregulated by corresponding overexpression plasmid. Cell viability was detected using CCK-8 assay. Cell invasion and migration were determined using transwell assay. Higher expression of PKM2 was observed in human gastric carcinoma cell lines MKN-45 and SGC-7901 than in the normal gastric mucosa epithelial cell line GES-1. PKM2 knockdown suppressed cancer cell invasion and migration and inhibited the epithelial-mesenchymal transition (EMT) phenotype by inhibiting E-cadherin and promoting vimentin and N-cadherin expression. Also, we observed that PKM2 knockdown suppressed the hypoxia-inducible factor alpha (HIF-1) and B-cell lymphoma 6 (BCL-6) signaling pathway. HIF-1 overexpression reversed the function of PKM2 silencing on cell invasion, migration, EMT, and BCL-6 expression. BCL-6 overexpression also reversed the function of PKM2 silencing on cell invasion, migration, and EMT but did not affect HIF-1 expression. Taken together, data from our study suggest that PKM2 knockdown impeded cell migration, invasion, and EMT of gastric carcinoma cells via the HIF-1/BCL-6 pathway.
胃癌是一种常见的恶性肿瘤。丙酮酸激酶 M2（PKM2）在癌症中高度表达，包括胃癌。然而，其在胃癌中的功能和分子机制尚不清楚。在这里，我们旨在探讨 PKM2 对胃癌恶性表型的功能和潜在机制。在这项研究中，通过定量实时 PCR 和 Western blot 分别检测了胃癌细胞系和正常胃黏膜上皮细胞系中 PKM2 的 mRNA 水平和蛋白水平。通过 siRNA 转染下调 PKM2。通过相应的过表达质粒上调 HIF-1 或 BCL-6。通过 CCK-8 测定法检测细胞活力。通过 Transwell 测定法测定细胞侵袭和迁移。与正常胃黏膜上皮细胞系 GES-1 相比，人胃癌细胞系 MKN-45 和 SGC-7901 中 PKM2 的表达水平更高。PKM2 敲低抑制了癌细胞的侵袭和迁移，并通过抑制 E-钙黏蛋白和促进波形蛋白和 N-钙黏蛋白的表达来抑制上皮-间充质转化（EMT）表型。此外，我们观察到 PKM2 敲低抑制了缺氧诱导因子 alpha（HIF-1）和 B 细胞淋巴瘤 6（BCL-6）信号通路。HIF-1 的过表达逆转了 PKM2 沉默对细胞侵袭、迁移、EMT 和 BCL-6 表达的作用。BCL-6 的过表达也逆转了 PKM2 沉默对细胞侵袭、迁移和 EMT 的作用，但不影响 HIF-1 的表达。综上所述，我们的研究数据表明，PKM2 敲低通过 HIF-1/BCL-6 通路阻碍了胃癌细胞的迁移、侵袭和 EMT。
