FTO-Mediated Downregulation of RAMP2-AS1 Promotes Glycolysis in Non-Small Cell Lung Cancer Cells by Inhibiting KLF9-Mediated Transcriptional Activation of LATS2
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS(2024)
Abstract
Background: Non-small cell lung cancer (NSCLC) is the most commonly occurring type of lung cancer. Previous studies have shown reduced expression of long noncoding RNA (lncRNA) RAMP2 antisense RNA1 ( RAMP2-AS1 ) in NSCLC; however, the mechanism of RAMP2-AS1 in NSCLC is not clear. Methods: Cell Counting Kit -8 was used to assess cell viability. Cell apoptosis was detected using flow cytometry. Western blot assay was used to examine protein levels. N6-methyladenosine (m 6 A)-RNA immunoprecipitation and Fluorescence in situ hybridization assays were used to detect the m 6 A modification and cellular location of RAMP2-AS1 , respectively. Glycolysis level was examined by commercial kits. Results: RAMP2-AS1 and large tumor suppressor 2 ( LATS2 ) were downregulated in NSCLC tissues. Knockdown of fat mass and obesity-associated protein ( FTO ) elevated the m 6 A modification RAMP2-AS1 . Overexpression of RAMP2-AS1 inhibited proliferation, glycolysis (indicated by high levels of glycolysis-related proteins, glucose consumption, lactate production, adenosine triphosphate content, and extracellular acidification rate) and induced cell apoptosis through Hippo signaling. RAMP2-AS1 transcriptionally activated LATS2 by binding with Kr & uuml;ppel-like factor 9 (KLF9). Downregulation of LATS2 reversed the suppressive impact of RAMP2-AS1 on cell glycolysis. Conclusion: FTO-mediated m 6 A demethylation of RAMP2-AS1 increased glycolysis by reducing the impact of KLF9 on LATS2 transcriptional activity. This study provides insights for developing novel therapeutic strategies for NSCLC.
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Key words
RAMP2-AS1,FTO,KLF9,LATS2,NSCLC
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