Niu Gengming, Deng Li, Zhang Xiaotian, Hu Zhiqing, Han Shanliang, Xu Ke, Hong Runqi, Meng He, Ke Chongwei
Department of General Surgery, the Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Shanghai, 200240, People's Republic of China.
Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
Open Med (Wars). 2020 Nov 21;15(1):1172-1183. doi: 10.1515/med-2020-0128. eCollection 2020.
Little is known about the functional roles of gamma-aminobutyric acid type A receptor subunit delta (GABRD) in colorectal cancer (CRC). The expression of GABRD between CRCs and adjacent normal tissues (NTs), metastasis and primary tumors was compared using public transcriptomic datasets. A tissue microarray and immunohistochemical staining (IHC) were used to determine the clinical and prognostic significance of the GABRD in CRC. We used gain-of-function and loss-of-function experiments to investigate the in vitro roles of GABRD in cultured CRC cells. We characterized the potential mechanism of GABRD's activities in CRC using a Gene Set Enrichment Analysis (GSEA) with The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset. We found that the GABRD expression was significantly increased in CRCs compared to that in NTs, but was similar between metastasis and primary tumors. Overexpression of GABRD was significantly associated with later pTNM stages and unfavorable patient survival. Overexpression of GABRD accelerated while knock-down of GABRD inhibited cell growth and migration. Mechanistically, the function of GABRD might be ascribed to its influence on major oncogenic events such as epithelial-mesenchymal transition (EMT), angiogenesis, and hedgehog signaling. Collectively, GABRD could be a novel prognostic predictor for CRC that deserves further investigation.
关于γ-氨基丁酸A型受体δ亚基（GABRD）在结直肠癌（CRC）中的功能作用，目前所知甚少。利用公开的转录组数据集比较了GABRD在结直肠癌组织与相邻正常组织（NTs）、转移灶与原发肿瘤之间的表达情况。采用组织芯片和免疫组化染色（IHC）来确定GABRD在结直肠癌中的临床和预后意义。我们通过功能获得和功能缺失实验来研究GABRD在培养的结直肠癌细胞中的体外作用。我们使用癌症基因组图谱结肠腺癌（TCGA-COAD）数据集，通过基因集富集分析（GSEA）来阐明GABRD在结直肠癌中发挥作用的潜在机制。我们发现，与正常组织相比，GABRD在结直肠癌中的表达显著增加，但在转移灶和原发肿瘤之间的表达相似。GABRD的过表达与较晚的pTNM分期和患者预后不良显著相关。GABRD的过表达促进了细胞生长和迁移，而敲低GABRD则抑制了细胞生长和迁移。从机制上讲，GABRD的功能可能归因于其对上皮-间质转化（EMT）、血管生成和刺猬信号等主要致癌事件的影响。总体而言，GABRD可能是一种值得进一步研究的新型结直肠癌预后预测指标。
