Ding Feng, Zhang Shuang, Gao Shaoyang, Shang Jian, Li Yanxia, Cui Ning, Zhao Qiu
Department of Gastroenterology/Hepatology, ZhongNan Hospital of Wuhan University, Wuhan 430071, China.
The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Oncotarget. 2017 Jul 22;8(38):64224-64236. doi: 10.18632/oncotarget.19451. eCollection 2017 Sep 8.
MORF4-related gene-binding protein (MRGBP), which is also known as chromosome 20 open reading frame 20 (C20orf20), is commonly highly expressed in several types of malignant tumors and tumor progression. However, the expression pattern and underlying mechanism of MRGBP in pancreatic ductal adenocarcinoma (PDAC) remain unknown. In the study, we found that MRGBP was frequently upregulated in PDAC tissues and cell lines. In addition, the upregulation of MRGBP was positively associated with TNM stage, T classification, and poor prognosis. Knockdown of MRGBP in the PDAC cell lines ASPC-1 and Mia PaCa-2 by transiently transfected with small interfering RNA (siRNA) drastically attenuated the proliferation, migration, and invasion of those cells, whereas ectopic MRGBP overexpression in BxPC-3 cells produced exactly the opposite effect. Furthermore, we also found that overexpression of MRGBP remarkably led to cell morphological changes and induced an increased expression of mesenchymal marker Vimentin, whereas a decreased expression of epithelial marker E-cadherin. Taken together, this study indicates that MRGBP acts as a tumor oncogene in PDAC and is a promising target of carcinogenesis.
MORF4相关基因结合蛋白（MRGBP），也被称为20号染色体开放阅读框20（C20orf20），在几种类型的恶性肿瘤及肿瘤进展中通常高度表达。然而，MRGBP在胰腺导管腺癌（PDAC）中的表达模式及潜在机制仍不清楚。在本研究中，我们发现MRGBP在PDAC组织和细胞系中经常上调。此外，MRGBP的上调与TNM分期、T分级及不良预后呈正相关。通过小干扰RNA（siRNA）瞬时转染在PDAC细胞系ASPC-1和Mia PaCa-2中敲低MRGBP，显著减弱了这些细胞的增殖、迁移和侵袭，而在BxPC-3细胞中异位过表达MRGBP则产生了完全相反的效果。此外，我们还发现MRGBP的过表达显著导致细胞形态改变，并诱导间充质标志物波形蛋白表达增加，而上皮标志物E-钙黏蛋白表达减少。综上所述，本研究表明MRGBP在PDAC中作为肿瘤癌基因发挥作用，是一个有前景的致癌靶点。
