Volume 28, No 5, May 2018
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 28 Issue 5, May 2018: 556-571
ORIGINAL ARTICLES
An NF90/NF110-mediated feedback amplification loop regulates dicer expression and controls ovarian carcinoma progression
Jérôme Barbier 1, Xin Chen 1,2, Gabriel Sanchez 1, Muyan Cai 2, Marion Helsmoortel 1, Takuma Higuchi 3, Pierre Giraud 1, Xavier Contreras 1,Gangjun Yuan 2, Zihao Feng 4, Rima Nait-Saidi 1, Olivier Deas 5, Lisa Bluy 1, Jean-Gabriel Judde 5, Sylvie Rouquier 1, William Ritchie6,Shuji Sakamoto 3 , Dan Xie 2 and Rosemary Kiernan 1
1 Institut de Génétique Humaine, CNRS, University of Montpellier, Gene Regulation Laboratory, 141 rue de la cardonille, Montpellier, France; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; 3Laboratory of Molecular Biology, Science Research Center, Kochi Medical School, Kochi University, Kochi 783-8505, Japan; 4The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510060, China; 5XenTech SAS, 4 rue Pierre Fontaine, Evry 91000, France and 6Institut de Génétique Humaine, CNRS, University of Montpellier, Machine Learning and Gene Regulation Laboratory, 141 rue de la cardonille, Montpellier 34396, France
Correspondence: Correspondence: Dan Xie (xiedan@sysucc.org.cn) or Rosemary Kiernan (Rosemary.Kiernan@igh.cnrs.fr)These authors contributed equally: Jérôme Barbier, Xin Chen and Gabriel Sanchez.
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.
doi:10.1038/s41422-018-0016-8
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