Fu Fangqiu, Wan Xuechao, Wang Dan, Kong Zhe, Zhang Yalong, Huang Wenhua, Wang Chenji, Wu Hai, Li Yao
Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai 200433, PR China.
Key Laboratory of Reproduction Regulation of NPFPC, Fudan University, Shanghai 200433, PR China.
Oncotarget. 2017 Dec 6;9(2):1931-1943. doi: 10.18632/oncotarget.23026. eCollection 2018 Jan 5.
Prostate cancer (PCa) is a leading cause of cancer-related deaths among males worldwide. However, the molecular mechanisms underlying the progression of PCa remain unclear. Despite several reported miRNAs in prostate cancer, these reports lacked system-level identification of differentially expressed miRNAs in large sample size. Moreover, it's still largely unknown how miRNAs result in tumorigenesis and progression of PCa. Therefore, by analyzing three public databases, we identified 16 upregulated miRNAs and 13 downregulated miRNAs, and validated miR-19a was one of the most upregulated miRNAs using qRT-PCR. The dual-luciferase reporter assays indicated VPS37A was a potential target of miR-19a. Functional assays revealed miR-19a served as an oncogene by inhibiting VPS37A. Notably, a significant inverse correlation of miR-19a and VPS37A expression was observed in PCa specimens. Moreover, miR-19a-high and VPS37A-low phenotypes were associated with poor prognosis with biochemical recurrence-free probability. In this study, we confirmed the oncogenic role of miR-19a via targeting VPS37A in PCa, identifying miR-19a and VPS37A as diagnosis and therapeutic biomarkers for PCa.
前列腺癌（PCa）是全球男性癌症相关死亡的主要原因。然而，PCa进展的分子机制仍不清楚。尽管已有多篇关于前列腺癌中miRNA的报道，但这些报道缺乏对大样本中差异表达miRNA的系统水平鉴定。此外，miRNA如何导致PCa的肿瘤发生和进展在很大程度上仍不清楚。因此，通过分析三个公共数据库，我们鉴定出16个上调的miRNA和13个下调的miRNA，并使用qRT-PCR验证miR-19a是上调最明显的miRNA之一。双荧光素酶报告基因实验表明VPS37A是miR-19a的潜在靶标。功能实验显示miR-19a通过抑制VPS37A发挥癌基因作用。值得注意的是，在PCa标本中观察到miR-19a和VPS37A表达呈显著负相关。此外，miR-19a高表达和VPS37A低表达表型与生化无复发生存概率的不良预后相关。在本研究中，我们证实了miR-19a通过靶向VPS37A在PCa中的致癌作用，确定miR-19a和VPS37A为PCa的诊断和治疗生物标志物。
