The human RNA surveillance factor Up-frameshift 1 inhibits hepatic cancer progression by targeting MRP2/ABCC2.
作者： Hai Zhang , Yina You , Zhongliang Zhu
DOI: 10.1016/J.BIOPHA.2017.05.090
关键词: Nonsense-mediated decay 、 Cancer stem cell 、 Ectopic expression 、 Apoptosis 、 Cancer research 、 Biology 、 Gene knockdown 、 Cancer 、 Viability assay 、 Stem cell
摘要: Although the roles of Up-frameshift 1 (UPF1) in hepatocellular carcinoma (HCC) have been partly revealed, detailed mechanisms remain poorly understood. Here, quantitative real-time PCR (qRT-PCR) and immunohistochemistry assays indicated that UPF1 expression was decreased HCC tissues compared to corresponding adjacent tissues, negatively correlated with MRP2/ABCC2 expression. Cell viability apoptosis analyses showed overexpression enhanced cell sensitivity sorafenib treatment, while knockdown sensitivity. Additionally, ectopic suppressed epithelial-mesenchymal transition (EMT) process generation cells stem properties. Mechanistically, directly bound ABCC2, increased nonsense-mediated mRNA decay (NMD) efficiency thus led downregualtion ABCC2. Collectively, functions as a tumor suppressor by preventing cancer (CSC)-like characteristics, inhibiting EMT enhancing chemotherapeutic via ABCC2 cells. These findings establish potential therapeutic target for patients.
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