lncRNA SNHG11 Promotes Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway and Oncogenic Autophagy.

Abstract

Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers, including gastric cancer (GC). Oncogenic autophagy is required for cancer cell survival. The present study aimed to investigate the regulatory role of lncRNA small nucleolar host gene 11 (SNHG11) in GC. We show that SNHG11 is upregulated in GC, and that its upregulation correlated with dismal patient outcomes. Functionally, SNHG11 aggravated oncogenic autophagy to facilitate cell proliferation, stemness, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in GC. Mechanistically, SNHG11 post-transcriptionally upregulated catenin beta 1 (CTNNB1) and autophagy related 12 (ATG12) through miR-483-3p/miR-1276, while the processing of precursor (pre-)miR-483/pre-miR-1276 was hindered by SNHG11. SNHG11 induced GSK-3β ubiquitination through interacting with Cullin 4A (CUL4A) to further activate the Wnt/β-catenin pathway. Intriguingly, SNHG11 regulated autophagy in a manner dependent on ATG12 rather than the Wnt/β-catenin pathway, whereas SNHG11 contributed to the malignant behaviors of GC cells via both pathways. Finally, SNHG11 upregulation in GC cells was shown to be transcriptionally induced by TCF7L2. In conclusion, we reveal that SNHG11 is an onco-lncRNA in GC and might be a promising prognostic and therapeutic target for GC.

• Authors: Qiong Wu, Jiali Ma, Jue Wei, Wenying Meng, Yugang Wang, Min Shi
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 29 Issue 3 Pg. 1258-1278 (03 03 2021) ISSN: 1525-0024 [Electronic] United States
• PMID: 33068778 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• ATG12 protein, human
• Autophagy-Related Protein 12
• Biomarkers, Tumor
• CTNNB1 protein, human
• CUL4A protein, human
• Cullin Proteins
• MIRN-1276 microRNA, human
• MIRN483 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• WNT1 protein, human
• Wnt1 Protein
• beta Catenin

Topics

• Animals
• Apoptosis
• Autophagy
• Autophagy-Related Protein 12 (genetics, metabolism)
• Biomarkers, Tumor (genetics, metabolism)
• Carcinogenesis
• Cell Proliferation
• Cullin Proteins (genetics, metabolism)
• Epithelial-Mesenchymal Transition
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• Prognosis
• RNA, Long Noncoding (genetics)
• Stomach Neoplasms (genetics, metabolism, pathology)
• Survival Rate
• Tumor Cells, Cultured
• Wnt1 Protein (genetics, metabolism)
• Xenograft Model Antitumor Assays
• beta Catenin (genetics, metabolism)