Aberrant expression of the pluripotency factor OCT4A in embryonal tumors of the central nervous system (CNS) is a key factor that contributes to tumor aggressiveness and correlates with poor patient survival. OCT4A overexpression has been shown to up-regulate miR-367, a microRNA (miRNA) that regulates pluripotency in embryonic stem cells and stem-like aggressive traits in cancer cells. Here, we show that (a) miR-367 is carried in microvesicles derived from embryonal CNS tumor cells expressing OCT4A; and (b) inhibition of miR-367 in these cells attenuates their aggressive traits. miR-367 silencing in OCT4A-overexpressing tumor cells significantly reduced their proliferative and invasive behavior, clonogenic activity, and tumorsphere generation capability. In vivo, targeting of miR-367 through direct injections of a specific inhibitor into the cerebrospinal fluid of Balb/C nude mice bearing OCT4A-overexpressing tumor xenografts inhibited tumor development and improved overall survival. miR-367 was also shown to target SUZ12, one of the core components of the polycomb repressive complex 2 known to be involved in epigenetic silencing of pluripotency-related genes, including POU5F1, which encodes OCT4A. Our findings reveal possible clinical applications of a cancer stemness pathway, highlighting miR-367 as a putative liquid biopsy biomarker that could be further explored to improve early diagnosis and prognosis prediction, and potentially serve as a therapeutic target in aggressive embryonal CNS tumors.

中文翻译：

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miR-367作为来自胚胎中枢神经系统肿瘤的干样细胞的治疗靶标。

多能性因子OCT4A在中枢神经系统（CNS）胚胎肿瘤中的异常表达是导致肿瘤侵袭性并与患者生存不良相关的关键因素。OCT4A过表达已显示出上调miR-367，这是一种微RNA（miRNA），可调节胚胎干细胞的多能性和癌细胞中的干样侵袭性特征。在这里，我们显示（a）miR-367携带在源自表达OCT4A的胚胎CNS肿瘤细胞的微泡中；（b）在这些细胞中对miR-367的抑制减弱了它们的侵袭性。过表达OCT4A的肿瘤细胞中的miR-367沉默显着降低了它们的增殖和侵袭行为，克隆形成活性和肿瘤球生成能力。体内，通过将特定的抑制剂直接注射到带有过量表达OCT4A的肿瘤异种移植物的Balb / C裸鼠的脑脊髓液中靶向miR-367可以抑制肿瘤的发展并提高总体生存率。还显示出miR-367靶向SUZ12，SUZ12是已知为参与多能性相关基因（包括编码OCT4A的POU5F1）的表观遗传沉默的多梳阻抑复合物2的核心成分之一。我们的发现揭示了癌症干性途径的可能临床应用，突出了miR-367作为公认的液体活检生物标志物，可以进一步探索该标志物以改善早期诊断和预后预测，并有可能作为侵袭性胚胎CNS肿瘤的治疗靶标。