Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance
Open Access
- 2 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogenesis
- Vol. 9 (3), 1-15
- https://doi.org/10.1038/s41389-020-0215-2
Abstract
Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and are frequently dysregulated in cancers. Here, we identify a critical lncRNA TRPM2-AS which is aberrantly expressed in gastric cancer (GC) tissues by screening The Cancer Genome Atlas Program(TCGA) database of GC cohort, and its upregulation is clinically associated with advanced pathologic stages and poor prognosis in GC patients. Silencing TRPM2-AS inhibits the proliferation, metastasis and radioresistance of GC cell whereas ectopic expression of TRPM2-AS significantly improves the progression of GC cell in multiple experiments. Mechanistically, TRPM2-AS serves as a microRNA sponge or a competitive endogenous RNA (ceRNA) for tumor suppressive microRNA miR-612 and consequently modulates the derepression of IGF2BP1 and FOXM1. Moreover, induced upregulation of IGF2BP1 subsequently increases the expression of c-Myc and promotes GC cell progression. Meanwhile, TRPM2-AS promotes the radioreistance of GC cell through enhancing the expression of FOXM1 as well. Thus, our findings support a new regulatory axis between TRPM2-AS, miR-612, IGF2BP1, or FOXM1 which serve as crucial effectors in GC tumorigenesis and malignant development, suggesting a promising therapeutic and diagnostic direction for GC.Keywords
This publication has 51 references indexed in Scilit:
- miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinomaThe Journal of Experimental Medicine, 2013
- CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression modelNucleic Acids Research, 2013
- Landscape of transcription in human cellsNature, 2012
- A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?Cell, 2011
- Emerging Roles for Natural MicroRNA SpongesCurrent Biology, 2010
- γH2AX foci analysis for monitoring DNA double-strand break repair: Strengths, limitations and optimizationCell Cycle, 2010
- Long non-coding RNAs: insights into functionsNature Reviews Genetics, 2009
- Identification of novel sense and antisense transcription at the TRPM2 locus in cancerCell Research, 2008
- CPC: assess the protein-coding potential of transcripts using sequence features and support vector machineNucleic Acids Research, 2007
- Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot projectNature, 2007