UNC50 Prompts G1/S Transition and Proliferation in HCC by Regulation of Epidermal Growth Factor Receptor Trafficking

Abstract

BackgroundUNC50 has long been recognized as a Golgi apparatus protein in yeast, and is involved in nicotinic receptor trafficking in Caenorhabditis elegans, but little is known about UNC50 gene function in human biology despite it being conserved from yeast to high eukaryotes.ObjectivesWe investigated the relation between UNC50 and human hepatocellular carcinoma (HCC) and the potential mechanisms underlying HCC development.Methods UNC50 mRNA expression patterns in 12 HCC and adjacent non-cancerous tissues determined using northern blotting were confirmed by real-time PCR in another 44 paired tissues. Microarray experiments were used to screen for global effects of UNC50 knockdown in the Hep3B cell line, and were confirmed by real-time PCR, western blotting, flow cytometry, and tetrazolium assay in both UNC50 overexpression and knockdown Hep3B cells.ResultsUNC50 expression levels were upregulated in HCC tissues in comparison with the adjacent non-cancerous tissues. UNC50 knockdown reduced mRNA levels of the downstream targets of the epidermal growth factor receptor (EGFR) pathway: cyclin D1 (CCND1), EGF, matrix metalloproteinase-7 (MMP7), aldose reductase-like 1 (AKR1B10), cell surface–associated mucin 1 (MUC1), and gastrin (GAST). Moreover, UNC50 influenced EGF, inducing cell cycle entry by affecting cell surface EGFR amounts.Conclusions UNC50 may plays some roles in HCC progression by affecting the EGFR pathway.

Upregulation of PP2Ac predicts poor prognosis and contributes to aggressiveness in hepatocellular carcinoma

“…28 BBC3 is a proapoptotic BH3-only protein that can sensitize HCC cells to sorafenib-induced apoptosis. 29 Some tumor-promoting genes such as MYC, 30 EGFR, 31 VEGFA, 32 and NOTCH1 33 are downregulated by PP2Ac silencing. These results offer a molecular insight into the regulation of the aggressiveness of HCC by PP2Ac.…”

Genome-wide siRNA screen identifies UNC50 as a regulator of Shiga toxin 2 trafficking

“…UNC50 now emerges as another protein that plays an important role in regulating GBF1 localization. The process by which these factors cooperatively mediate membrane recruitment of GBF1 under physiological conditions as well as the consequences of changes in activities or levels of one or more of these factors in disease states (e.g., up-regulation of UNC50 in hepatocellular carcinoma; Fang et al, 2015 ) on GBF1 function is another important area of future research.…”

Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing

“…UNC50 has long been recognized as a Golgi apparatus protein in yeast, and is involved in nicotinic receptor trafficking in Caenorhabditis elegans. In 2015, Fang et al found that UNC50 was correlated with G1/S transition and proliferation in hepatocellular carcinoma via the influencing epidermal growth factor receptor trafficking (47). Interestingly, our data showed that UNC50 was involved with the nigericin damage, which could be cis-regulated by lnc-SLC25A3-3_1.…”