Aberrant microRNA (miRNA) expression is a central hallmark of hepatocellular carcinoma (HCC) and identification of the mechanisms underlying the miRNA actions should provide invaluable resource for revealing the molecular basis of different malignant behaviors in HCC. Previous high-throughput analysis has identified miR-767-5p as a unique miRNA signature of HCC, but the biological relevance and corresponding molecular basis of miR-767-5p in HCC is still in its infancy. The current study was, therefore, designed to elucidate whether changes in miR-767-5p expression levels affect HCC pathogenesis, and to further identify the putative targets. miR-767-5p expression was observed to be upregulated by ~ 3.7-fold in surgical HCC specimens as compared to that in adjacent normal hepatic tissues, and this up-regulation trend correlated well to disease progression and predicted a poor prognosis in HCC patients. Functionally, miR-767-5p-overexpressing cells had a significantly higher proliferative, migratory, and invasive potential, and exhibited an enhanced anchorage-dependent clonogenesis and a tumor formation potential in vivo. Mechanistically, PMP22, a core component of integral membrane glycoprotein of peripheral nervous system myelin, was further identified as a direct down-stream target of miR-767-5p in HCC cells. Conversely, stable ectopic expression of PMP22 abrogated the promoting effects of miR-767-5p on HCC aggressive phenotype. Collectively, the available data suggest that as a potent oncomiR, miR-767-5p actions along HCC progression are in part mediated by its function as a posttranscriptional repressor of PMP22 signaling.

中文翻译：

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miR-767-5p在肝细胞癌进展过程中的功能分析及其失调的临床意义。

microRNA（miRNA）的异常表达是肝细胞癌（HCC）的中心标志，对miRNA作用基础的机制的鉴定应为揭示HCC中不同恶性行为的分子基础提供宝贵的资源。先前的高通量分析已将miR-767-5p确定为HCC的独特miRNA标志，但是miR-767-5p在HCC中的生物学相关性和相应的分子基础仍处于起步阶段。因此，当前的研究旨在阐明miR-767-5p表达水平的变化是否影响HCC发病机理，并进一步确定推定的靶标。观察到，与邻近的正常肝组织相比，外科HCC标本中的miR-767-5p表达上调了约3.7倍，而且这种上调趋势与疾病进展密切相关，并预测HCC患者的预后不良。在功能上，miR-767-5p过表达的细胞具有明显更高的增殖，迁移和侵袭潜能，并在体内表现出增强的锚定依赖性克隆形成和肿瘤形成潜能。从机制上讲，PMP22是外周神经系统髓磷脂整体膜糖蛋白的核心成分，被进一步鉴定为HCC细胞中miR-767-5p的直接下游靶标。相反，PMP22的稳定异位表达消除了miR-767-5p对HCC侵袭性表型的促进作用。总的来说，可用数据表明，作为有效的oncomiR，miR-767-5p沿着HCC进展的作用部分地由其作为PMP22信号传导的转录后阻遏物起作用。