Home Neoplasma Ahead of print Neoplasma Vol.69, No.6, p. 1338–1348, 2022

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ISSN 0028-2685
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Neoplasma Vol.69, No.6, p. 1338–1348, 2022

Title: PRKAA1, stabilized by FTO in an m6A-YTHDF2-dependent manner, promotes cell proliferation and glycolysis of gastric cancer by regulating the redox balance
Author: Yangmei Zhang, Xichang Zhou, Xue Cheng, Xiou Hong, Xiaowei Jiang, Guilong Jing, Kai Chen, Yang Li

Abstract: Gastric carcinoma (GC) is the fourth most common malignancy worldwide and the second cause of death of all malignancies worldwide. AMPK catalytic subunit α1 (PRKAA1) is involved in various types of cancer and PRKAA1 knockdown significantly decreased the invasiveness of GC cells. Fat mass and obesity-associated protein (FTO)-regulation of m6A has been shown to be involved in different diseases including cancer. However, the role of PRKAA1 and m6A modification in GC remains to be elucidated. PRKAA1 was silenced or overexpressed to study the role of PRKAA1 in regulating cell viability, colony formation, and glycolysis. Levels of lactic acid, GSH, and NADP+/NADPH were measured using commercial kits. Extracellular acidification rates were determined by an extracellular flux analyzer. RNA immunoprecipitation was performed to test m6A levels and the interaction between PRKAA1-3'-UTR and YTHDF2. Quantitative RT-PCR and immunoblots were applied to measure mRNA or protein levels, respectively. PRKAA1 silencing inhibited cell growth, colony formation, and glycolysis but enhanced apoptosis, while the PRKAA1 overexpression promoted cell growth, colony formation, and glycolysis but inhibited apoptosis of GC cells. Data also indicated that PRKAA1 regulated cell growth and apoptosis by regulating the redox balance. Mechanism study demonstrated that FTO regulated PRKAA1 mRNA m6A modification and stability. Clinical samples analysis demonstrated that PRKAA1 and FTO expression were increased in GC patients and positively correlated with each other. FTO increased levels of PRKAA1 by regulating its mRNA m6A modification and stability. PRKAA1, in turn, promoted cell viability, colony formation, and glycolysis but inhibited apoptosis of GC cells by promoting the redox balance.

Keywords: redox balance; N6-methyladenosine; gastric carcinoma; PRKAA1; glycolysis; apoptosis
Published online: 28-Oct-2022
Year: 2022, Volume: 69, Issue: 6 Page From: 1338, Page To: 1348
doi:10.4149/neo_2022_220714N714


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