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

Background UNC50 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. Objectives We 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. Results UNC50 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.

• Publication year

  2015

• Venue

  PLoS ONE

• Publication date

  2015-03-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0119338PMID 25738771PMCID 4349650
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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