Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3 expression
Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3 expression
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Dicer 的缺失通过提高 PDIA3 表达促进上皮性卵巢癌进展
DOI：
10.1007/s13277-016-5218-4
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发表时间：
2016-10-01
期刊：
影响因子：
--
通讯作者：
Wang, Zehua
中科院分区：
文献类型：
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作者：
Zhu, Ying;Cai, Liqiong;Wang, Zehua
Dicer是microRNA （miRNA）加工机制的重要组成部分，其低表达与上皮性卵巢癌的晚期和不良临床结果相关。为了研究Dicer在上皮性卵巢癌中的功能相关性，并鉴定其下游效应物，采用二维凝胶电泳结合质谱法进行蛋白质组学分析。Dicer的缺失促进了卵巢癌细胞的增殖和迁移，并伴随着蛋白质的全球上调。共鉴定出26个蛋白，其中7个上调，19个下调。用生物信息学方法分析了鉴定蛋白的功能及其相互作用。其中，蛋白二硫异构酶A3 （PDIA3）被认为是Dicer的潜在靶蛋白。siRNA抑制PDIA3可显著缓解Dicer耗竭介导的增殖和迁移促进作用。此外，在Dicer缺失的细胞中，靶向PDIA3的mirna减少。总之，低Dicer表达通过提高PDIA3表达促进上皮性卵巢癌的进展。
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.