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

In this study, the researchers investigated the role of NORAD in gastric cancer (GC) and found that it acts as an oncogene by regulating KMT2D expression and mediating the PTEN/PI3K/AKT signaling pathway. These findings suggest that NORAD could be a potential therapeutic target for GC.