LncRNA NORAD mediates KMT2D expression by targeting miR-204-5p and affects the growth of gastric cancer

Background: Long non-coding ribonucleic acids ( lncRNAs) are a class of non-coding RNAs implicated in the development of many malignancies, including gastric cancer (GC). In this study, we investigated the functions and molecular mechanisms of non-coding RNA activated by deoxyribonucleic acid damage (NORAD) in GC. Methods: NORAD expression at the messenger RNA levels was determined by quantitative reverse transcriptase ( RT)- polymerase chain reaction assays. Cell proliferation, migration, and invasion were detected by Cell Counting Kit-8 assays, in-vivo tumor formation assays, and Transwell assays. Cell-cycle distribution was detected by a flow cytometry analysis. NORAD location was detected by nucleocytoplasmic fractionation assays. The interaction between NORAD and the microRNA-204-5p (miR-204-5p)/Lysine Methyltransferase 2D (KMT2D) axis was verified by dual-luciferase reporter gene assays and RNA binding protein immunoprecipitation (RIP) assays. Western blot was used to study the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT) signaling pathway. Results: NORAD was upregulated in the GC tissues and cell lines. The silencing of NORAD repressed cell proliferation and the Growth 2 (G2)/Mitosis (M) cell-cycle transition in GC. NORAD also regulated KMT2D expression by targeting miR-204-5p and mediated PTEN/PI3K/AKT signaling in GC. Conclusions: We found that NORAD acts as an oncogene in GC. Our findings might provide a novel therapeutic target for GC.

Automated summary

The study revealed that NORAD functions as an oncogene in gastric cancer, potentially through regulating the miR-204-5p/KMT2D axis and PTEN/PI3K/AKT signaling pathway.