LncRNA SNHG11 facilitates tumor metastasis by interacting with and stabilizing HIF-1?.

Epigenetic alteration is one of the hallmarks of colorectal cancer (CRC). Many driver genes are regulated by DNA methylation in CRC. However, the role of DNA methylation regulating lncRNAs remain elusive. Here, we identify that SNHG11 (small nucleolar RNA host gene 11) is upregulated by promotor hypomethylation in CRC and ...
is associated with poor prognosis in CRC patients. SNHG11 can promote CRC cell migration and metastasis under hypoxia. Interestingly, the DNA-binding motif of SNHG11 is similar to that of HIF-1?. In addition, SNHG11-associated genes are enriched with members of the HIF-1 signaling pathway in CRC. Mechanistically, SNHG11 binds to the pVHLrecognition sites on HIF-1?, thus blocking the interaction of pVHL with HIF-1? and preventing its ubiquitination and degradation. Moreover, SNHG11 upregulates the expression of HIF-1? target genes, i.e., AK4, ENO1, HK2, and Twist1. Notably, SNHG11 can bind to the HRE sites in the promoter of these genes and increase their transcription. In summary, these results identify a SNHG11/ HIF-1? axis that plays a pivotal role in tumor invasion and metastasis.
Mesh Terms:
Animals, Cell Hypoxia, Cell Line, Tumor, Cell Movement, Cohort Studies, Colorectal Neoplasms, DNA Methylation, Disease Progression, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Male, Mice, Middle Aged, Neoplasm Invasiveness, Neoplasm Metastasis, Prognosis, Promoter Regions, Genetic, Protein Stability, RNA, Long Noncoding, Signal Transduction, Transcriptional Activation, Von Hippel-Lindau Tumor Suppressor Protein, Xenograft Model Antitumor Assays
Oncogene
Date: Dec. 01, 2019
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