On October 18 of the America Eastern Standard Time, Jiang Qiuhi Research Group and Wu Shourong Research Group from the School of Bioengineering of Chongqing University publish a research paper titled “Identification of XBP1-u as a novel regulator of the MDM2/p53 axis using an shRNA library” on Science Advances (subordinate to Science) released by American Association for the Advancement of Science (AAAS). The paper is drawing extensive attention from media at home and abroad after its publication.

A cell cycle refers to the process from completion of one round of cell division to the end of the next round. The irregular cell cycle is closely related to various diseases. In particular, the loss of control of cell cycle will result in unlimited growth of cells, which will then lead to tumor. The tumor suppressor gene p53 and its upstream regulatory factor MDM2 play a key role in regulation of cell cycle. p53 helps to suppress progress of cell cycle and MDM2 expedites degradation of p53 protein through ubiquitination, thus promoting the progress of the cell cycle.

In the research, the shRNA plasmid library was used for high throughput screening, and it was found that the XBP1 played a very important role in regulating the tumor cell cycle. XBP1 has two isomers, namely, spliceosome XBP1-s and non-spliceosome XBP1-u. Generally, the endoplasmic reticulum stress will cause XBP1-u to be spliced into spliceosome XBP1-s, which is responsible for removing unfolded protein which is bad for cells. A lot of studies mainly focused on the biological function of spliceosome XBP1-s, and tended to ignore the non-spliceosome XBP1-u. This research discovered that the scarcely concerned non-spliceosome XBP1-u would stabilize MDM2 protein through suppressing self-ubiquitination of MDM2 expedite degradation of tumor-inhibiting factor p53 protein. It was also found that the XBP1-u was of high expression in the tumor tissue, and XBP1-u suppression remarkably reduced the formation capacity of animal tumor. The research revealed the important regulating mechanism of XBP1-u for MDM2/p53 signal channel, and is of great significance for molecular mechanism analysis of genesis and development of tumors and clinical diagnosis and treatment of tumors.

It is the first time that the regulatory mechanism of p53 has been studied in the world and therefore it is of extraordinary potential significance. The research findings explained the new molecular regulation mechanism of tumor-inhibiting factor p53 in genesis and development of tumors, and identified the direction for targeted therapy of tumor in precision medicine, and also laid a solid theoretical foundation for development and preparation of targeted anti-cancer drugs. It is the first time that Chongqing  University has issued a research paper as the first organization and an independent communication organization on the subordinate of Science in the biomedical domain. The research has been completed under the lead of Professor Jiang Qihui and Professor Wu Shourong from the School of Bioengineering of Chongqing University, and has been supported by University of Tokyo, Chongqing Cancer  Hospital and National Institute of Advanced Industrial Science and Technology of Japan. The first author of the paper is Huang Can, a doctoral candidate of 2015 of the School of Bioengineering.

The research findings, after published, have been drawing extensive attention from the media. Websites and media, including Xinhua News Agency, Science and Technology Daily, China News Service, Chongqing Daily, CQNews, Chongqing Morning News, Chongqing Evening News, Chongqing Commercial Daily, Chongqing Times, and cq.qq.com, have interviewed the authors of the paper. Click the following links to know more.

China News:

http://dw.chinanews.com/chinanews/content.jsp?id=8356484&classify=zw&pageSize=6&language=chs

CSTNet

http://www.stdaily.com/index/kejixinwen/2017-10/19/content_585450.shtml?from=singlemessage&isappinstalled=0#10006-weixin-1-52626-6b3bffd01fdde4900130bc5a2751b6d1

Xinhua News Agency:

https://news.sina.cn/2017-10-19/detail-ifymzqpq2526898.d.html?from=wap

Chongqing Evening News:

http://mxwapp.cqwb.com.cn/news/app/share/newsDetail.html?newsInId=386145937217026

CQNews:

http://h5.cqliving.com/info/detail/999986.html?cid=999986&f=20

The research has been funded by Natural Science Foundation of China, Chongqing Natural Science Foundation, basic scientific research operating expense for colleges and universities from the central finance, and the Postgraduate Scientific Research Innovation Project of Chongqing.

The research findings exchange and report meeting is held by Faculty of Sciences holds on October 20. Xia Zhining, deputy dean of the Faculty of Sciences, presides over the meeting. Officials of the School of Bioengineering, doctors from Chongqing Cancer Hospital, and teachers and students from the School of Life Science and the School of Pharmaceutical Sciences are present and participate in the discussion.

Link of the paper:

Can Huang, Shourong Wu, Hong Ji, Xuesong Yan, Yudan Xie, Saomi Murai, Hezhao Zhao, Makoto Miyagishi, Vivi Kasim. Science Advances, 2017, Vol. 3, no. 10, e1701383. DOI: 10.1126/sciadv.1701383

http://advances.sciencemag.org/content/3/10/e1701383