Department of Biliary and Pancreatic Surgery/Cancer Research Center, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
J Cell Physiol. 2020 Mar;235(3):2506-2520. doi: 10.1002/jcp.29155. Epub 2019 Sep 11.
Ras converting enzyme 1 (Rce1) plays an important role in invasion and metastasis of malignancy. However, the mechanism has not yet been fully explored in hepatocellular carcinoma (HCC). Primarily, we investigated the expression of Rce1 and H-Ras influence on patient prognosis through the clinical data. Further, we analyzed the regulatory effects of Rce1/H-Ras signal pathway on the epithelial-mesenchymal transition (EMT) in vitro and in vivo. Finally, we screened out the protein which bonds with Rce1 by CO-IP experiment to discuss the mechanism of Rce1 in EMT of HCC. This research revealed a significantly decreased expression of Rce1 in HCC compared with noncancerous tissues (p < .05). In contrast, H-Ras expression was increased in the tumor. The expression of them was a close association with the differentiation and tumor-node-metastasis (TNM) stage of the tumor (p < .001; p = .035, respectively) and Rce1 was an independent prognostic indicator (95%Cl: 0.193-0.821; p = .013). Through targeted regulation of Rce1 by cDNA or small interfering RNA, results show that the lower expression of Rce1 facilitated EMT and promoted the invasion and metastasis of HCC (p < .05). Furthermore, the CO-IP experiment unfolded that Rce1 could bond with farnesyltransferase-β (FNTB) which mediated the expression of H-Ras. Conclusions: Rce1 inhibits EMT via target regulation H-Ras and suppress the early invasion and metastasis of HCC. It may be a potential therapeutic target and prognostic indicator for HCC.
Ras 转换酶 1（Rce1）在恶性肿瘤的侵袭和转移中发挥重要作用。然而，其在肝细胞癌（HCC）中的作用机制尚未完全阐明。首先，我们通过临床数据研究了 Rce1 的表达和 H-Ras 对患者预后的影响。进一步，我们分析了 Rce1/H-Ras 信号通路对体外和体内上皮-间充质转化（EMT）的调节作用。最后，我们通过 CO-IP 实验筛选出与 Rce1 结合的蛋白，以探讨 Rce1 在 HCC EMT 中的作用机制。该研究显示 HCC 组织中 Rce1 的表达明显低于非癌组织（p<.05）。相反，肿瘤中 H-Ras 的表达增加。它们的表达与肿瘤的分化和肿瘤-淋巴结-转移（TNM）分期密切相关（p<.001；p=.035），Rce1 是独立的预后指标（95%Cl：0.193-0.821；p=.013）。通过 cDNA 或小干扰 RNA 对 Rce1 进行靶向调控，结果表明 Rce1 表达下调促进 EMT，并促进 HCC 的侵袭和转移（p<.05）。此外，CO-IP 实验表明 Rce1 可以与法呢基转移酶-β（FNTB）结合，后者介导 H-Ras 的表达。结论：Rce1 通过靶向调控 H-Ras 抑制 EMT，抑制 HCC 的早期侵袭和转移。它可能是 HCC 的潜在治疗靶点和预后指标。
