Recently, the team led by Professor Liu Qingguang from Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi 'an Jiaotong University (XJTU) published an article entitled "Histone citrullination by PADI4 is required for HIF-dependent transcriptional responses to hypoxia and tumor vascularization" in Science Advances (a top journal among AREA 1 of Chinese Academy of Sciences with an impact factor of 14.132).

The research team led by Professor Liu Qingguang cooperated with their counterparts led by Professor Gregg L. Semenza from Johns Hopkins University School of Medicine, laureate of 2019 Nobel Prize in Physiology or Medicine, elected member of National Academy of Sciences, National Academy of Medicine and American Academy of Arts and Sciences to innovatively demonstrate that PADI4 expression is induced by hypoxia in a HIF-dependent manner in breast cancer and hepatocellular carcinoma cells. PADI4, in turn, is recruited by HIFs to hypoxia response elements (HREs) and is required for HIF target gene transcription. Hypoxia induces histone citrullination at HREs that is PADI4 and HIF dependent. RNA sequencing revealed that almost all HIF target genes in breast cancer cells are PADI4 dependent. In addition, PADI4 is required for breast and liver tumor growth and angiogenesis in mice. PADI4 expression is correlated with HIF-1α expression and vascularization in human breast cancer biopsies. The findings in this study indicate that the research and development of small molecule inhibitors targeting HIF and/or PADI4 activities may be a novel therapeutic strategy for patients with breast cancer and hepatocellular carcinoma.

In recent years, Professor Liu Qingguang's team has been devoted to the basic-clinical-translational research and disciplinary construction of tumor microenvironment, highlighted the training and cultivation of clinical and scientific research thinking of postgraduate students, adopted the novel training mode of clinical practice followed by basic research, and obtained multiple scientific research achievements with application prospects in clinical practice.

Wang Yufeng, a doctoral student from Department of Hepatobiliary Surgery of our hospital is the first author. Tu Kangsheng, an associate research fellow from our hospital is the co-author. Professor Liu Qingguang and Professor Gregg L. Semenza are co-corresponding authors of this article.

Article link:

https://advances.sciencemag.org/content/7/35/eabe3771

https://pubmed.ncbi.nlm.nih.gov/34452909/