====== ROBO1 ======


Roundabout homolog 1 is a protein that in humans is encoded by the ROBO1 gene

===== Function =====

Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror-image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The protein encoded by ROBO1 is structurally similar to a Drosophila integral membrane protein which is encoded by the Drosophila roundabout gene (a member of the immunoglobulin gene superfamily) and is both an axon guidance receptor and a cell adhesion receptor, known to be involved in the decision by axons to cross the central nervous system midline. Two transcript variants encoding different isoforms have been found for ROBO1.
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MicroRNA-588 and its potential target Roundabout-directed receptor 1 ([[ROBO1]]) have been reported to promote [[tumor invasion]] and [[proliferation]] in diseases such as gastric, pancreatic, and [[hepatocellular carcinoma]], while their function in GBM and response to hypoxic states remain elusive.

A [[microarray]] was leveraged to identify differentially expressed [[microRNA]]s in [[U251]] [[glioma cell]]s [[culture]]d under normoxic and hypoxic conditions. The expression of miR-588 was assessed using quantitative real-time [[PCR]] (qRT‒PCR). Gain- and loss-of-function studies were used to evaluate the role of miR-588 under hypoxic and normoxic conditions. [[Cell invasion]], [[migration]], [[proliferation]], and vasculogenic mimicry (VM) formation experiments were performed. The relationship between miR-588 and ROBO1 was confirmed using western blot and luciferase reporter assays. Intracranial xenograft tumor mouse models were used to study the function of miR-588 in vivo.

Results: The expression of miR-588 was significantly upregulated in hypoxic glioma cells relative to normoxic glioma cells. miR-588 inhibited the invasive, migratory, and VM-forming abilities of glioma cells in vitro and in vivo. Mechanistically, roundabout guidance receptor 1 (ROBO1) is a direct, functionally relevant target of miR-588 in glioma. ROBO1 knockdown suppressed the expression of matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9), thereby inhibiting the invasive, migratory, and VM-forming abilities of glioma.

Conclusions: MiR-588 regulated the behaviors of hypoxic glioma cells by targeting ROBO1. miR-588 can be used as a prognostic marker for glioma and has potential implications in glioma [[gene therapy]]
((Yu R, Zhao R, Sun X, Zhang Z, Wang S, Gao X, Sun Z, Xue H, Li G. MicroRNA-588 regulates the invasive, migratory and vasculogenic mimicry-forming abilities of hypoxic glioma cells by targeting ROBO1. Mol Biol Rep. 2022 Dec 2. doi: 10.1007/s11033-022-08063-z. Epub ahead of print. PMID: 36459288.)).