PIGT promotes cell growth, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking

• Published in: Journal of translational medicine Vol. 22; no. 1; p. 5
• Main Authors: Tan, Mingyue, Pan, Qi, Yu, Chao, Zhai, Xinyu, Gu, Jianyi, Tao, Le, Xu, Dongliang
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.01.2024; BioMed Central; BMC
• Subjects: Acidification; Analysis; Bioengineering; Biotechnology; Bladder cancer; Breast cancer; Care and treatment; Cell cycle; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Development and progression; Diagnosis; Gene expression; Genetic aspects; Glucose; Glucose metabolism; Glucose transporter; Glucose transporter 1; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Glycolysis; Glycolysis - genetics; Glycosylation; Glycosylphosphatidylinositol; Growth; Health aspects; Humans; Instrument industry; Invasiveness; Laboratory animals; Liver cancer; Membrane trafficking; Metastases; Metastasis; Methylation; Methyltransferases; mRNA; N6-methyladenosine; Oxidative phosphorylation; Oxygen consumption; phosphatidylinositol Glycan Anchor Biosynthesis Class T; Phosphorylation; Protein binding; Protein transport; RNA; RNA methylation; RNA modification; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - metabolism; Scientific equipment and supplies industry; Tumorigenesis; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; China; United States; United States > US; Glycolysis; Glucose transporter 1; phosphatidylinositol Glycan Anchor Biosynthesis Class T; Bladder cancer; RNA methylation
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-023-04805-0

Bladder cancer is very common worldwide. PIGT is a subunit of the glycosylphosphatidylinositol transamidase which involves in tumorigenesis and invasiveness. m6A modification of mRNA has been linked to cell proliferation, tumor progression and other biological events. However, how PIGT is regulated and what is the function of PIGT in bladder cancer remains to be elucidated. PIGT was silenced or overexpressed to study its role in regulating bladder cancer. Cell proliferation and invasion were examined with the Cell Counting Kit-8, colony formation and Transwell assay, respectively. Cellular oxygen consumption rates or extracellular acidification rates were detected by a XF24 Analyzer. Quantitative RT-PCR and immunoblots were performed to detect mRNA and protein levels. PIGT was overexpressed in bladder cancer. Silencing PIGT inhibited cell proliferation, oxidative phosphorylation, and glycolysis. Overexpressing PIGT promoted cell proliferation, oxidative phosphorylation, glycolysis in vitro and tumor metastasis in vivo by activating glucose transporter 1 (GLUT1). PIGT also promoted GLUT1 glycosylation and membrane trafficking. Wilms' tumor 1-associated protein (WTAP) mediated PIGT m6A modification, and m6A reader, insulin-like growth factor 2 mRNA-binding protein (IGF2BP2), binds to the methylated PIGT to promote the stability of PIGT, leading to up-regulation of PIGT. WTAP mediates PIGT m6A modification to increase the stability of PIGT via the IGF2BP2, which enhances cell proliferation, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking.