Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3 expression
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Dicer is an essential component of the microRNA (miRNA) processing machinery whose low expression is associated with advanced stage and poor clinical outcome in epithelial ovarian cancer. To investigate the functional relevance of Dicer in epithelial ovarian cancer and to identify its downstream effectors, two-dimensional gel electrophoresis combined with mass spectrometry was used for proteomic profiling. Dicer depletion promoted ovarian cancer cell proliferation and migration accompanied by a global upregulation of proteins. Twenty-six proteins, 7 upregulated and 19 downregulated, were identified. The functions of the identified proteins and their interactions were bioinformatically analyzed. Among them, protein disulfide-isomerase A3 (PDIA3) was considered to be a potential target protein of Dicer. PDIA3 repression by siRNA could significantly relieve the proliferation- and migration-promoting effect mediated by Dicer depletion in vitro and in vivo. Moreover, the miRNAs targeting PDIA3 were decreased in cells with Dicer depletion. In summary, low Dicer expression contributes to epithelial ovarian cancer progression by elevating PDIA3 expression.
KeywordsDicer Ovarian cancer Two-dimensional electrophoresis MicroRNA PDIA3
Jing Cai and Zehua Wang conceived and designed the research. Ying Zhu and Liqiong Cai performed the experiments and analyzed the data. Na Chen, Xiaoqing Yi, Jing Guo, and Yong Zhao provided administrative and technical support. Ying Zhu wrote the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
This work was supported by the National Natural Science Foundation of China (Nos. 81502248 and 81572572).
Conflicts of interest
All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committee of the Tongji Medical College, Huazhong University of Science and Technology.
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