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Abstract：
Medulloblastoma (MB), a prevalent pediatric central nervous system tumor, is influenced by microRNAs (miRNAs) that impact tumor initiation and progression. However, the specific involvement of miRNAs in MB tumorigenesis remains unclear. Using single-cell RNA sequencing, we identified ROR2 expression in normal human fetal cerebellum. Subsequent analyses, including immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blot, assessed ROR2 expression in MB tissues and cell lines. We investigated miR-124-3p and miR-194-5p and their regulatory role in ROR2 expression through the dual-luciferase reporter, qRT-PCR, and western blot assays. Mechanistic insights were gained through functional assays exploring the impact of miR-124-3p, miR-194-5p, and ROR2 on MB growth in vitro and in vivo. We observed significantly reduced miR-124-3p and miR-194-5p expression and elevated ROR2 expression in MB tissues and cell lines. High ROR2 expression inversely correlated with overall survival in WNT and SHH subgroups of MB patients. Functionally, overexpressing miR-124-3p and miR-194-5p and inhibiting ROR2 suppressed in vitro malignant transformation and in vivo tumorigenicity. Mechanistically, miR-124-3p and miR-194-5p synergistically regulated the ROR2/PI3K/Akt pathway, influencing MB progression. Our findings indicate that miR-124-3p and miR-194-5p function as tumor suppressors, inhibiting MB progression via the ROR2/PI3K/Akt axis, suggesting a key mechanism and therapeutic targets for MB patients.
摘要：
髓母细胞瘤(MB),一种常见的小儿中枢神经系统肿瘤,受影响肿瘤起始和进展的微小RNA(miRNA)的影响。然而,miRNAs在MB肿瘤发生中的特异性参与尚不清楚.使用单细胞RNA测序，我们确定了正常人胎儿小脑中ROR2的表达。随后的分析，包括免疫荧光，实时定量PCR(qRT-PCR),和蛋白质印迹,评估MB组织和细胞系中的ROR2表达。我们通过双荧光素酶报告基因研究了miR-124-3p和miR-194-5p及其在ROR2表达中的调节作用。qRT-PCR,和蛋白质印迹分析。通过探索miR-124-3p的影响的功能测定获得了机制见解，miR-194-5p,和ROR2对MB体外和体内生长的影响。我们在MB组织和细胞系中观察到miR-124-3p和miR-194-5p表达显着降低，ROR2表达升高。在WNT和SHH亚组的MB患者中，高ROR2表达与总生存期呈负相关。功能上,过表达miR-124-3p和miR-194-5p并抑制ROR2抑制了体外恶性转化和体内致瘤性。机械上,miR-124-3p和miR-194-5p协同调控ROR2/PI3K/Akt通路,影响MB进展。我们的发现表明miR-124-3p和miR-194-5p作为肿瘤抑制因子，通过ROR2/PI3K/Akt轴抑制MB进展，提示MB患者的关键机制和治疗目标。
