5 years ago

Up-regulated WDR5 promotes gastric cancer formation by induced cyclin D1 expression

Mingkai Liu, Fuchao Guo, Wei Sun
Gastric cancer (GC) is the fourth common cancer and second leading cause of cancer-related mortality in the world. WD repeat domain 5 (WDR5) has been identified that its functions as an important role in various biological functions through the epigenetic regulation of gene transcription. However, the oncogenic effect of WDR5 in gastric cancer remains largely unknown. In this study, we investigated the role of WDR5 in gastric cancer genesis. We found that WDR5 expression is increased in gastric cancer patients. Through survival analysis, we found that high expression of WDR5 is associated with high risk gastric cancer; patients who with WDR5 high expression have poor survival rate compared with those who with WDR5 low expression. To make further investigation, we identified that WDR5 is targeted for cell cycle arrest by the Cyclin D1 in a process that is regulated by H3K4me3. Moreover, over-expression of WDR5 promotes cell proliferation, induces S/G2/M arrest in cell cycle, and promotes the expression of WDR5 targets, as well as that of H3K4me3 on the promoter of its targets. Inversely, WDR5 knockdown by shRNA inhibits cell proliferation, reverses S/G2/M arrest in cell cycle, and suppresses the expression of WDR5 targets, as well as that of H3K4me3. We also observed the positive correlation of WDR5 expression with its target in the cohort study of gastric patients. Taken together, our data reveal that WDR5 may have oncogenic effect and WDR5-mediated H3K4 methylation plays an important role in gastric cancer. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26491

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.