00085472can160356-sup-161941_2_supp_3649818_scsjpy.docx (24.98 kB)
Supplementary Figure Legends from LncRNA HOXA11-AS Promotes Proliferation and Invasion of Gastric Cancer by Scaffolding the Chromatin Modification Factors PRC2, LSD1, and DNMT1
journal contribution
posted on 2023-03-31, 00:21 authored by Ming Sun, Fengqi Nie, Yunfei Wang, Zhihong Zhang, Jiakai Hou, Dandan He, Min Xie, Lin Xu, Wei De, Zhaoxia Wang, Jun WangLegend for Supplementary Figures S1-S6.
Funding
National Natural Science Foundation of China
Key Clinical Medicine Technology Foundation of Jiangsu Province
Jiangsu Provincial Developing Health Project
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ARTICLE ABSTRACT
Long noncoding RNAs (lncRNA) have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we investigated lncRNA alterations that contribute to gastric cancer through an analysis of The Cancer Genome Atlas RNA sequencing data and other publicly available microarray data. Here we report the gastric cancer–associated lncRNA HOXA11-AS as a key regulator of gastric cancer development and progression. Patients with high HOXA11-AS expression had a shorter survival and poorer prognosis. In vitro and in vivo assays of HOXA11-AS alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, and apoptosis. Strikingly, high-throughput sequencing analysis after HOXA11-AS silencing highlighted alterations in cell proliferation and cell–cell adhesion pathways. Mechanistically, EZH2 along with the histone demethylase LSD1 or DNMT1 were recruited by HOXA11-AS, which functioned as a scaffold. HOXA11-AS also functioned as a molecular sponge for miR-1297, antagonizing its ability to repress EZH2 protein translation. In addition, we found that E2F1 was involved in HOXA11-AS activation in gastric cancer cells. Taken together, our findings support a model in which the EZH2/HOXA11-AS/LSD1 complex and HOXA11-AS/miR-1297/EZH2 cross-talk serve as critical effectors in gastric cancer tumorigenesis and progression, suggesting new therapeutic directions in gastric cancer. Cancer Res; 76(21); 6299–310. ©2016 AACR.Usage metrics
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Keywords
BiomarkersCancer InterceptionBiomarkers and interventionCancer PreventionEarly DetectionDrug TargetsOncoprotein & tumor suppressor drug targetsGastrointestinal CancersStomach cancerGene RegulationAntisense control of gene expressionPosttranscriptional and translational controlOncogenes & Tumor Suppressors
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