Medical College, Guangxi University, Nanning 530004, China.
Department of Pathology, the first Medical Center of PLA General Hospital, Beijing, China.
Gene. 2022 May 30;825:146436. doi: 10.1016/j.gene.2022.146436. Epub 2022 Mar 15.
Hepatocellular carcinoma (HCC) is one of the lethal malignancies worldwide. Tumor metastasis is the main cause of HCC related death. Although progress has been made in the mechanism study of HCC in the past decades, the underlying mechanism of HCC metastasis has not been fully illustrated. In the present study, bioinformatic analysis including weighted gene co-expression network analysis (WGCNA), differentially expressed gene analysis, and gene enrichment analysis were applied to discover genes correlated with HCC metastasis. Immunohistochemistry (IHC) assays were applied to detect the expression of NPNT in HCC samples. Cell transfection, wound healing, matrigel transwell assays, and western blot assays were utilized to evaluate the effects of NPNT on cell migration and invasion and signaling pathway variation. We found that NPNT was up-regulated in HCC tumor tissues compared with normal tissues. Especially, NPNT was highly expressed in metastatic tumor compared with non-metastatic HCC tumors. Down-regulation of NPNT via siRNA transfection inhibited cell migration, invasion, and FAK/PI3K/AKT signaling pathway in HCC. Our results demonstrate that NPNT is a potential key regulator in HCC metastasis.
肝细胞癌 (HCC) 是全球致死率较高的恶性肿瘤之一。肿瘤转移是 HCC 相关死亡的主要原因。尽管在过去几十年中，HCC 的机制研究已经取得了进展，但 HCC 转移的潜在机制尚未完全阐明。在本研究中，我们应用了生物信息学分析，包括加权基因共表达网络分析 (WGCNA)、差异表达基因分析和基因富集分析，以发现与 HCC 转移相关的基因。免疫组织化学 (IHC) 检测用于检测 NPNT 在 HCC 样本中的表达。细胞转染、划痕愈合、基质胶 Transwell 检测和 Western blot 检测用于评估 NPNT 对细胞迁移和侵袭以及信号通路变化的影响。我们发现，NPNT 在 HCC 肿瘤组织中的表达高于正常组织。特别是，NPNT 在转移性肿瘤中的表达高于非转移性 HCC 肿瘤。通过 siRNA 转染下调 NPNT 抑制了 HCC 中的细胞迁移、侵袭和 FAK/PI3K/AKT 信号通路。我们的结果表明，NPNT 是 HCC 转移的潜在关键调节因子。
