An NF90/NF110-mediated feedback amplification loop regulates dicer expression and controls ovarian carcinoma progression
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.
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We thank V.N. Kim for pFlag-DROSHA, C. Basler for pFlag-DRBP76, Feng Zhang for pSpCas9BB-2A-GFPPX458, Addgene plasmid # 48138;members ofthe labs for helpful discussions. J.B. and G.S. were supported by ANRS and ERC, X.C. by CNRS, FRM FDT20111223640 and NSFC, M.H. and P.G. by ERC and L.B. by FRM. This work was supported by grants from the National Key R&D Program of China no. 2017YFC1309001 and no.2016YFC1302305 to D.X.,
2018-08-28（万方平台首次上网日期，不代表论文的发表时间）
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