LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern

  • Cancer Discov. 2016 Jul;6(7):784-801. doi: 10.1158/2159-8290.CD-15-0921.
Tian-Tian Sun  1 ,  Jie He  2 ,  Qian Liang  1 ,  Lin-Lin Ren  1 ,  Ting-Ting Yan  1 ,  Ta-Chung Yu  1 ,  Jia-Yin Tang  1 ,  Yu-Jie Bao  1 ,  Ye Hu  1 ,  Yanwei Lin  3 ,  Danfeng Sun  3 ,  Ying-Xuan Chen  1 ,  Jie Hong  4 ,  Haoyan Chen  4 ,  Weiping Zou  5 ,  Jing-Yuan Fang  4
Affiliations
  • 1. State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
  • 2. Department of Gastroenterology and Guangzhou Key Laboratory of Digestive Disease, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
  • 3. State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan.
  • 4. State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. [email protected] [email protected] [email protected] [email protected].
  • 5. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan. [email protected] [email protected] [email protected] [email protected].
PMID: 27147598 DOI: 10.1158/2159-8290.CD-15-0921
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.

Significance: 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.