Abstract
Long noncoding RNAs (lncRNA) play a role in carcinogenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown. In this study, we identified a novel lncRNA, GClnc1, which was upregulated and associated with tumorigenesis, tumor size, metastasis, and poor prognosis in gastric cancer. GClnc1 affected gastric cancer cell proliferation, invasiveness, and metastasis in multiple gastric cancer models. Mechanistically, 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. Thus, GClnc1 is mechanistically, functionally, and clinically oncogenic in gastric cancer. Targeting GClnc1 and its pathway may be meaningful for treating patients with gastric cancer. This report documents a novel lncRNA, GClnc1, which may act as a scaffold to recruit the WDR5 and KAT2A complex and modify the transcription of target genes. This study reveals that GClnc1 is an oncogenic lncRNA in human gastric cancer. Cancer Discov; 6(7); 784-801. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 681.
Highlights
Gastric cancer is the fourth most diagnosed type of cancer and the third most common cause of cancer-related death worldwide [1, 2]
We found that eight candidate Long noncoding RNAs (lncRNA) were significantly increased in gastric cancer tissues compared with adjacent normal tissues (Supplementary Table S1)
Multiple oncogenic pathways may contribute to gastric cancer carcinogenesis [40, 41]; the potential involvement of lncRNAs is poorly defined in human gastric cancer
Summary
Gastric cancer is the fourth most diagnosed type of cancer and the third most common cause of cancer-related death worldwide [1, 2]. Patients with advanced gastric cancer have a poor prognosis [3, 4]. Pathologic classification is used to assess prognosis and inform the treatment of gastric cancer. Massive efforts have been made to develop the noninvasive biomarkers to detect early cancer and/or reflect an individual’s cancer risk, which is essential to reducing gastric cancer mortality [5]. There has been little success in improving the disease-free survival rate of patients. Because the pathologic mechanisms of gastric cancer progression are not fully understood, more research is needed to discover and develop effective biomarkers and targets for gastric cancer diagnosis and treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
