Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PRChina.
Department of Neurosurgery, Suining Central Hospital, Suining, PR China.
Int J Neurosci. 2024 Sep;134(9):991-1002. doi: 10.1080/00207454.2023.2201873. Epub 2023 Apr 20.
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. 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. 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 and xenograft assays . To determine the targeting relationship between miR-106a-5p and GPR133, a dual-luciferase reporter assay was conducted. 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. 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.
神经胶质瘤是最常见的恶性脑肿瘤。GPR133 是神经胶质瘤进展的关键因素。然而，GPR133 在神经胶质瘤侵袭和 EMT 中的作用以及与之相关的 microRNAs（miRNAs）仍知之甚少。本研究旨在阐明 miR-106a-5p 和 GPR133 在神经胶质瘤中的生物学功能以及它们相互作用的分子机制。通过实时定量聚合酶链反应（qRT-PCR）分析神经胶质瘤标本和细胞中 miR-106a-5p 和 GPR133 的 mRNA 表达。通过 Western blot 测定 GPR133 蛋白水平和侵袭和 EMT 相关蛋白水平。通过细胞计数试剂盒-8（CCK-8）、Transwell、划痕愈合、集落形成实验和异种移植实验测定 miR-106a-5p 和 GPR133 在神经胶质瘤细胞中的功能。通过双荧光素酶报告基因实验确定 miR-106a-5p 和 GPR133 之间的靶向关系。在神经胶质瘤细胞和标本中观察到 miR-106a-5p 表达明显降低。miR-106a-5p 高表达的患者预后良好，而 GPR133 高表达的患者 OS 较短。此外，过表达 miR-106a-5p 或下调 GPR133 抑制神经胶质瘤细胞的进展。此外，miR-106a-5p 通过结合其 3'-UTR 负调控 GPR133 表达，并通过靶向 GPR133 抑制神经胶质瘤细胞的侵袭、迁移、增殖和 EMT。miR-106a-5p 是一种肿瘤抑制因子，负调控 GPR133。miR-106a-5p/GPR133 轴可能成为神经胶质瘤的治疗靶点。
