LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern
| Autor: | Lin Lin Ren, Yu Jie Bao, Jing-Yuan Fang, Tingting Yan, Weiping Zou, Jie He, Yanwei Lin, Jiayin Tang, Ta Chung Yu, Ying Xuan Chen, Danfeng Sun, Tian-Tian Sun, Haoyan Chen, Jie Hong, Ye Hu, Qian Liang |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Chromatin Immunoprecipitation medicine.disease_cause Bioinformatics Models Biological Metastasis Epigenesis Genetic Histones 03 medical and health sciences Mice 0302 clinical medicine Stomach Neoplasms Cell Line Tumor medicine WDR5 Animals Cluster Analysis Humans Gene Regulatory Networks Histone methyltransferase complex Histone Acetyltransferases biology Superoxide Dismutase Gene Expression Profiling Intracellular Signaling Peptides and Proteins Computational Biology High-Throughput Nucleotide Sequencing Histone acetyltransferase Histone-Lysine N-Methyltransferase medicine.disease Tumor Burden Gene expression profiling Disease Models Animal 030104 developmental biology Histone Cell Transformation Neoplastic Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Disease Progression Heterografts RNA Long Noncoding Carcinogenesis Chromatin immunoprecipitation Protein Binding |
| Zdroj: | Cancer discovery. 6(7) |
| ISSN: | 2159-8290 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|