MICU1 is a mitochondrial inner membrane protein that inhibits mitochondrial calcium entry; elevated MICU1 expression is characteristic of many cancers, including ovarian cancer. MICU1 induces both glycolysis and chemoresistance and is associated with poor clinical outcomes. However, there are currently no available interventions to normalize aberrant MICU1 expression. Here, we demonstrate that microRNA‐195‐5p (miR‐195) directly targets the 3′ UTR of the MICU1 mRNA and represses MICU1 expression. Additionally, miR‐195 is under‐expressed in ovarian cancer cell lines, and restoring miR‐195 expression reestablishes native MICU1 levels and the associated phenotypes. Stable expression of miR‐195 in a human xenograft model of ovarian cancer significantly reduces tumor growth, increases tumor doubling times, and enhances overall survival. In conclusion, miR‐195 controls MICU1 levels in ovarian cancer and could be exploited to normalize aberrant MICU1 expression, thus reversing both glycolysis and chemoresistance and consequently improving patient outcomes.

中文翻译：

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MicroRNA-195 控制卵巢癌中 MICU1 的表达和肿瘤生长。

MICU1是一种线粒体内膜蛋白，抑制线粒体钙进入；MICU1 表达升高是许多癌症的特征，包括卵巢癌。MICU1 诱导糖酵解和化疗耐药，并与不良的临床结果相关。然而，目前没有可用的干预措施来使异常的 MICU1 表达正常化。在这里，我们证明 microRNA-195-5p (miR-195) 直接靶向 MICU1 mRNA 的 3' UTR 并抑制 MICU1 表达。此外，miR-195 在卵巢癌细胞系中表达不足，恢复 miR-195 表达可重建天然 MICU1 水平和相关表型。miR-195 在人类卵巢癌异种移植模型中的稳定表达可显着减少肿瘤生长、增加肿瘤倍增时间并提高总体生存率。总之，miR-195 控制卵巢癌中的 MICU1 水平，可用于使异常的 MICU1 表达正常化，从而逆转糖酵解和化疗耐药，从而改善患者的预后。