An NF90/NF110-mediated feedback amplification loop regulates dicer expression and controls ovarian carcinoma progression

Autor: Sylvie Rouquier, Muyan Cai, Pierre Giraud, Rosemary Kiernan, Lisa Bluy, Olivier Deas, Gabriel Sanchez, Shuji Sakamoto, Jean Gabriel Judde, William Ritchie, Xavier Contreras, Dan Xie, Jérôme Barbier, Xin Chen, Gangjun Yuan, Rima Nait-Saidi, Takuma Higuchi, Zi-Hao Feng, Marion Helsmoortel
Přispěvatelé: Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Laboratory of Molecular Biology, Science Research Center, Kochi Medical School, Kochi University, Kochi, 783-8505, Japan, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510060, China, XenTech SAS, 4 rue Pierre Fontaine, Evry, 91000, France
Rok vydání: 2017
Předmět:
Zdroj: Cell Research
Cell Research, Nature Publishing Group, 2018, 28 (5), pp.556-571. ⟨10.1038/s41422-018-0016-8⟩
ISSN: 1748-7838
1001-0602
Popis: International audience; 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.
Databáze: OpenAIRE