Jingyuan Fang’s team from Renji Hospital publish the latest research results in "Cancer Discovery"

Recently, the American Cancer Society (AACR)'s top journal "Cancer Discovery" (the latest impact factor is 19.8 points) published the cooperative research results entitled "LncRNA (Lactobacillus) GClnc1 promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern" by Shanghai Jiao Tong University School of Medicine affiliated Renji Hospital and University of Michigan. The article also received a commentary by invited editor of the same issue. The correspondent authors of this article are Professor Jingyuan Fang, Associate Private Investigator Jie Hong and Haoyan Chen from Department of Gastroenterology of Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, and Professor Weiping Zou from University of Michigan. The first author is PHD graduate Tiantian Sun supervised by Professor Jingyuan Fang.
According to the correspondent author of this article, Professor Jingyuan Fang, Director of Department of Gastroenterology from Renji Hospital, the pathologic mechanisms of gastric cancer progression are very complex. Currently, world-wide research is focusing on early warning of gastric cancer, prognosis prediction, as well as discovery of new targets for prevention and treatment of gastric cancer. Although it is known that long non-coding RNA (lncRNA) can be widely involved in tumorigenesis and progression through multiple modes of action, the function of lncRNAs in human gastric cancer remains largely unknown. The clinical significance of this study includes three aspects. First, it’s firstly reported that lncRNA GClnc1 can be a separate biomarker to predict the occurrence and prognosis of gastric cancer. Second, it’s firstly found that the expression of lncRNA GClnc1 was gradually increased in the progression of gastric cancer from mild, median to severe precancerous lesion. The specificity of lncRNA detection was better than that of traditional techniques, suggesting that the predictive factor could be one of the independent diagnostic criteria for progression of precancerous lesion of gastric cancer. Third, the study found for the first time that the lncRNA GClnc1 can be used to predict prognosis of gastric cancer patients independent of TNM staging. Compared to the generally used TNM staging for prognosis prediction of conventional tumor, this study revealed that the expression of GClnc1 may be determined to predict the prognosis of cancer patients.
Jingyuan Fang’s team concluded that, through the transcriptome array analysis, they firstly discovered that lncRNA GClnc1 is overexpressed in gastric cancer tissue. Clinical analysis showed that GClnc1 expression positively correlated with pathologic differentiation, tumor size and vascular invasion, revealing the overexpression of GClnc1 is closely related to the poor prognosis of gastric cancer. Further investigation revealed that GClnc1 bound WDR5 (a key component of histone methyltransferase complex) and KAT2A histone acetyltransferase, acted as a modular scaffold of WDR5 and KAT2A complexes, coordinated their localization, specified the histone modification pattern on the target genes, including SOD2, and consequently altered gastric cancer cell biology.

This study was the first to discover the role of lncRNA GClnc1 in the development and progression of gastric cancer and it provide an important new idea for the development of new anti-tumor drugs. Professor Fang’s team will continue to find more lncRNAs, which are likely to participate in the tumorigenesis of digestive tract tumors, so that to find more breakthroughs and hope for the diagnosis and treatment of gastrointestinal cancers. This study was supported by grants from NSFC Innovative Research Group Project, the NSFC International Cooperation and Exchange Project, the NSFC Excellent Youth Scholars, the NSFC Surface Project and others. The first author and the main authors are all from Department of Gastroenterology of Renji Hospital. (Correspondent Qixia Wang / Reporter Huiyun Yuan / Translator Weiwei Zhang)