scholarly journals RNA Interference of IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Cell Proliferation and Invasion in Breast Carcinoma Cells

Author(s):  
Gaowu Hu ◽  
Ye Xu ◽  
Wenquan Chen ◽  
Jiandong Wang ◽  
Chunying Zhao ◽  
...  

Breast cancer is a highly prevalent disease affecting women. The association of IQ motif containing GTPase-activating protein 3 (IQGAP3) and breast cancer is poorly defined. Here we reported that IQGAP3 is a key regulator of cell proliferation and metastasis during breast cancer progression. The expression of IQGAP3 was significantly increased in breast tissues compared to nontumor tissues at both protein and mRNA levels. Furthermore, IQGAP3 had a high expression level in ZR-75-30 and BT474 compared to other breast cancer cell lines. Depletion of IQGAP3 through RNA interference in ZR-75-30 and BT474 significantly inhibited cell proliferation. More importantly, IQGAP3 silencing in breast cancer cells notably repressed cell migration and invasion. Further analysis suggested that inhibition of cell proliferation and metastasis was associated with some proteins, including p53, MMP9, Snail, CDC42, p-ERK1/2, KIF2C, KIF4A, PCNA, and Twist. Since expression of IQGAP3 seems to be associated with the pathogenesis of breast cancer and suppression of it can inhibit cancer cell growth and metastasis, IQGAP3 may be a potential therapeutic target in human breast cancer.

2020 ◽  
Author(s):  
Yonglei Liu ◽  
Yanfei Yang ◽  
Junxian Du ◽  
Dong Lin ◽  
Feng Li

Abstract Background Exosomes carrying microRNA (miRNAs) mediate cell to cell communication which are important regulators in cancer growth and progression. However, the roles and molecular mechanism of the miRNAs in the exosomes from carcinoma associated fibroblasts (CAFs) are still not clear. Methods The targeted gene of miR-3613-3p was predicted by TargetScan and miRanda. The proliferation of cancer cells was conducted by cell counting kit-8 and colony formation assay. Cancer cell migration and invasion were measured by wound healing assay and Transwell assays respectively. Luciferase activity was assayed by dual luciferase assay system. miRNA and mRNA expression was measured by real time RT-PCR. SOCS2 protein levels was assayed by western blotting. Results It was verified that miR-3613-3p was up-regulated in exosomes from fibroblasts educated by TGF-β1, breast cancer cells and breast cancer tissues. Exosomal miR-3613-3p promoted breast cancer cell proliferation and metastasis. Loss-of-function experiments revealed that miR-3613-3p down-regulation in the CAFs exosomes suppressed cell proliferation and drug resistance in breast cancer by targeting SOCS2 expression. The clinical data showed that miR-3613-3p was negatively related to SOCS2 in breast cancer tissues. Conclusion These findings demonstrated that activated fibroblasts exosomes with high levels of miR-3613-3p played an oncogenic role in breast cancer cell survival, metastasis and drug responses, which suggested that the oncogenic role of miR-3613-3p in breast cancer progression.


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