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Updated: Mar 16, 2026
Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression
Published on: August 28, 2012
Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3 expression
Ying Zhu1, Liqiong Cai1, Jing Guo1
1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, China.
Abstract:
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.
Insights
Low Dicer expression in epithelial ovarian cancer promotes tumor growth and spread. This occurs by increasing protein disulfide-isomerase A3 (PDIA3) levels, a key driver of cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Dicer is crucial for microRNA (miRNA) processing and its low expression correlates with advanced epithelial ovarian cancer (EOC) and poor prognosis.
- Understanding Dicer's functional role and downstream targets in EOC is vital for therapeutic development.
Purpose of the Study:
- To investigate the functional significance of Dicer in epithelial ovarian cancer.
- To identify downstream protein effectors regulated by Dicer in EOC.
Main Methods:
- Proteomic profiling using two-dimensional gel electrophoresis and mass spectrometry was employed.
- Bioinformatic analysis was used to assess protein functions and interactions.
- Small interfering RNA (siRNA) was utilized to deplete Dicer and PDIA3.
Main Results:
- Dicer depletion enhanced EOC cell proliferation and migration, with global protein upregulation observed.
- Twenty-six differentially expressed proteins were identified, including upregulated protein disulfide-isomerase A3 (PDIA3).
- PDIA3 repression counteracted the effects of Dicer depletion, and miRNAs targeting PDIA3 were reduced upon Dicer depletion.
Conclusions:
- Low Dicer expression contributes to epithelial ovarian cancer progression.
- Elevated PDIA3 expression, driven by reduced Dicer levels, is a key mechanism in EOC advancement.
- Dicer may regulate PDIA3 expression through miRNA pathways, offering potential therapeutic targets.
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