Department of Pathology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Xiangya Medical School, Central South University, Changsha, Hunan, China.
Life Sci. 2021 Jul 15;277:119462. doi: 10.1016/j.lfs.2021.119462. Epub 2021 Apr 5.
Mammalian/mechanistic target of rapamycin (mTOR) is essential in the progression of pancreatic adenocarcinoma (PAAD). But the role of Ras homolog enriched in brain (RHEB), a key activator of mTORC1, is unclear in this disease. This work aims to clarify the function of RHEB in PAAD.
A pan-cancer analysis of RHEB was conducted by using data from several public available databases. Immunohistochemical (IHC) staining on a tissue microarray was used to validate the expression of RHEB in PAAD. In vitro experiments were conducted to explore the function of RHEB in the disease. An integrated bioinformatics tools were used to understand the mechanism of RHEB and construct a RHEB-related prognostic signature.
RHEB was significantly overexpressed in PAAD and high expression of the gene was associated with poor prognosis. RHEB promoted proliferation, migration and invasion of pancreatic cancer cells. Gene set enrichment analysis (GSEA) showed that RHEB participated in cell cycle progression and WNT signaling pathway. A RHEB-related prognostic signature was developed, and PAAD patients with high risk score had a significantly shorter overall survival.
RHEB was up-regulated in PAAD and might be a useful therapeutic target.
哺乳动物雷帕霉素靶蛋白（mTOR）在胰腺导管腺癌（PAAD）的进展中起着至关重要的作用。但是，Ras 同源物富集在脑（RHEB）作为 mTORC1 的关键激活物，在这种疾病中的作用尚不清楚。本研究旨在阐明 RHEB 在 PAAD 中的功能。
通过使用来自多个公共可用数据库的数据，对 RHEB 进行了泛癌症分析。通过组织微阵列的免疫组织化学（IHC）染色来验证 RHEB 在 PAAD 中的表达。进行了体外实验以探索 RHEB 在该疾病中的功能。使用综合的生物信息学工具来了解 RHEB 的机制并构建 RHEB 相关的预后特征。
RHEB 在 PAAD 中显著过表达，并且该基因的高表达与预后不良相关。RHEB 促进了胰腺癌细胞的增殖、迁移和侵袭。基因集富集分析（GSEA）表明 RHEB 参与了细胞周期进程和 WNT 信号通路。开发了一个 RHEB 相关的预后特征，高风险评分的 PAAD 患者的总生存期明显缩短。
RHEB 在 PAAD 中上调，可能是一个有用的治疗靶点。
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