Institut de Génétique Humaine, CNRS, University of Montpellier, Gene Regulation Laboratory, 141 rue de la cardonille, Montpellier, France.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Cell Res. 2018 May;28(5):556-571. doi: 10.1038/s41422-018-0016-8. Epub 2018 Mar 21.
Reduced expression of DICER, a key enzyme in the miRNA pathway, is frequently associated with aggressive, invasive disease, and poor survival in various malignancies. Regulation of DICER expression is, however, poorly understood. Here, we show that NF90/NF110 facilitates DICER expression by controlling the processing of a miRNA, miR-3173, which is embedded in DICER pre-mRNA. As miR-3173 in turn targets NF90, a feedback amplification loop controlling DICER expression is established. In a nude mouse model, NF90 overexpression reduced proliferation of ovarian cancer cells and significantly reduced tumor size and metastasis, whereas overexpression of miR-3173 dramatically increased metastasis in an NF90- and DICER-dependent manner. Clinically, low NF90 expression and high miR-3173-3p expression were found to be independent prognostic markers of poor survival in a cohort of ovarian carcinoma patients. These findings suggest that, by facilitating DICER expression, NF90 can act as a suppressor of ovarian carcinoma.
DICER，一种 miRNA 通路中的关键酶，其表达水平降低通常与多种恶性肿瘤中侵袭性强、浸润性强和预后不良有关。然而，DICER 表达的调控机制尚不清楚。本研究表明，NF90/NF110 通过控制 miR-3173 的加工来促进 DICER 的表达，miR-3173 嵌入 DICER pre-mRNA 中。由于 miR-3173 反过来靶向 NF90，因此建立了一个反馈放大环来控制 DICER 的表达。在裸鼠模型中，NF90 的过表达降低了卵巢癌细胞的增殖，显著减少了肿瘤大小和转移，而 miR-3173 的过表达则以 NF90 和 DICER 依赖的方式显著增加了转移。临床研究发现，在卵巢癌患者队列中，低 NF90 表达和高 miR-3173-3p 表达是预后不良的独立预测标志物。这些发现表明，NF90 通过促进 DICER 的表达，可以作为卵巢癌的抑制因子。
