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Overexpression and biological function of IQGAP3 in human pancreatic cancer
Weihong Xu1, Bin Xu1, Yiting Yao1
1Department of Clinical Laboratory of Tongren Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, China.
Abstract:
IQGAP3 (IQ motif containing GTPase activating protein3) belongs to IQGAP family. Recent studies have investigated that IQGAP3 was overexpressed in several tumor tissues. This study was designed to explore the expression and role of IQGAP3 in pancreatic cancer, a highly lethal disease. IQGAP3 mRNA expression was significantly increased in pancreatic cancer tissues, compared with non-cancerous tissues. Moreover, its expression was strongly associated with tumor size, differentiation, lymph node metastasis and patients' overall survival. Gene set enrichment analysis (GSEA) on The Cancer Genome Atlas (TCGA) dataset showed that cell apoptosis, metastasis and Cdc42 pathways were strongly associated with IQGAP3 expression in pancreatic cancer patients. Knocking down of IQGAP3 in two pancreatic cancer cell lines with high level of IQGAP3 (BXPC-3 and SW1990) significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis. Moreover, silencing of IQGAP3 also affected the expression of cell apoptosis-, metastasis- and Cdc42 pathway-related proteins. Cdc42 knockdown had similar inhibitory effects on the cellular behavior of BXPC-3 cells. In conclusion, IQGAP3 may act as an oncogene in pancreatic cancer through regulating Cdc42 expression. Our data suggest IQGAP3 might be a novel diagnostic marker and therapeutic target for this cancer.
Insights
IQGAP3 (IQ motif containing GTPase activating protein3) is overexpressed in pancreatic cancer, promoting tumor growth and metastasis. Reducing IQGAP3 inhibits cancer progression and may offer a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- IQGAP3 (IQ motif containing GTPase activating protein3) is increasingly recognized for its role in various cancers.
- Pancreatic cancer remains a highly lethal disease with limited effective therapeutic options.
Purpose of the Study:
- To investigate the expression and functional role of IQGAP3 in pancreatic cancer.
- To explore IQGAP3 as a potential diagnostic marker and therapeutic target for pancreatic cancer.
Main Methods:
- Analysis of IQGAP3 mRNA expression in pancreatic cancer tissues versus non-cancerous tissues.
- Gene Set Enrichment Analysis (GSEA) using The Cancer Genome Atlas (TCGA) dataset.
- In vitro experiments involving IQGAP3 knockdown in pancreatic cancer cell lines (BXPC-3 and SW1990).
Main Results:
- IQGAP3 mRNA expression was significantly elevated in pancreatic cancer tissues and correlated with tumor size, differentiation, lymph node metastasis, and patient survival.
- GSEA indicated associations between IQGAP3 expression and cell apoptosis, metastasis, and Cdc42 pathways.
- IQGAP3 knockdown suppressed proliferation, migration, and invasion while inducing apoptosis in pancreatic cancer cells, affecting related protein expressions.
- Cdc42 knockdown mimicked the inhibitory effects of IQGAP3 knockdown on cell behavior.
Conclusions:
- IQGAP3 functions as an oncogene in pancreatic cancer, potentially by regulating Cdc42 expression.
- IQGAP3 represents a promising novel diagnostic marker and therapeutic target for pancreatic cancer.
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