Targeting GPR133 via miR-106a-5p inhibits the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of glioma cells

• Published in: International journal of neuroscience 2024-09, Vol.ahead-of-print (ahead-of-print), p.1-12
• Main Authors: Zhang, Shiyuan, Zhang, Yuan, Sun, Xiaochuan
• Format: Article
• Language: English
• Subjects: Animals; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Movement - physiology; Cell Proliferation - physiology; EMT; Epithelial-Mesenchymal Transition - genetics; Epithelial-Mesenchymal Transition - physiology; Female; Gene Expression Regulation, Neoplastic; glioma; Glioma - genetics; Glioma - metabolism; Glioma - pathology; GPR133; Humans; invasion; Male; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; miR-106a-5p; Neoplasm Invasiveness - genetics; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism
• ISSN: 0020-7454; 1563-5279; 1563-5279; 1543-5245
• DOI: 10.1080/00207454.2023.2201873

Background: Glioma is the most common malignant brain tumor. GPR133 is a key factor in the progression of glioma. However, the role of GPR133 in glioma invasion and EMT and the microRNAs (miRNAs) associated with this pathway are still poorly understood.Objective: This study aims to elucidate the biological function of miR-106a-5p and GPR133 in glioma as well as the molecular mechanism of their interaction.Methods: The mRNA expression of miR-106a-5p and GPR133 in glioma specimens and cells was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The protein level of GPR133 and the levels of invasion- and EMT-related proteins were measured by western blotting. miR-106a-5p and GPR133 function in glioma cells was determined through cell counting kit-8 (CCK-8), transwell, wound healing, colony formation assays in vitro and xenograft assays in vivo. To determine the targeting relationship between miR-106a-5p and GPR133, a dual-luciferase reporter assay was conducted.Results: A marked reduction in miR-106a-5p expression was observed in glioma cells and specimens. Patients with high expression of miR-106a-5p had a good prognosis, while patients with high expression of GPR133 had a shorter OS. Additionally, overexpression of miR-106a-5p or downregulation of GPR133 inhibited the progression of glioma cells. Furthermore, miR-106a-5p negatively regulated GPR133 expression by binding to its 3′-UTR, and restrained the invasion, migration, proliferation and EMT of glioma cells by targeting GPR133.Conclusions: miR-106a-5p is a tumor suppressor that negatively regulates GPR133. The miR-106a-5p/GPR133 axis could potentially serve as a therapeutic target for glioma.