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IQGAP1 gene silencing induces apoptosis and decreases the invasive capacity of human hepatocellular carcinoma cells

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Tumor Biology

Abstract

IQ motif-containing GTPase-activating proteins (IQGAPs) belong to a conserved family, and they are involved in various intracellular processes. IQGAP1 is expressed in all cells, while IQGAP2 and IQGAP3 are mainly expressed in hepatic cells. IQGAP1 has been suggested to be an oncogene, while IQGAP2 is considered a tumor-suppressor gene. However, the relationship between RAS family genes and IQGAP genes remains unclear. We recently demonstrated this interaction in a chemically induced mouse liver cancer. In this study, IQGAP1 expression was partially silenced in human hepatocellular carcinoma (HepG2) cells. We investigated the impact of IQGAP1 silencing on the interactions of IQGAP and RAS with several apoptotic proteins, including caspase-3 (CASP3), BCL2-associated X protein (BAX), and B-cell leukemia/lymphoma 2 (BCL2). Additionally, we investigated the effects of the interactions of these genes on cell viability, proliferation, apoptosis, and invasive capacity. IQGAP1 siRNA-treated HepG2 cells showed lower invasive capacity than the control cells, and this reduction was time- and vector concentration-dependent. In addition, IQGAP1 silencing resulted in significantly lower IQGAP1 level and subsequently higher IQGAP2 and IQGAP3 expression in HepG2 cells than in the control. Flow cytometry analyses indicated that the silencing of IQGAP1 can induce early and late apoptosis in HepG2 cells. Additionally, IQGAP2, IQGAP3, CASP3, and BAX were upregulated whereas IQGAP1 and BCL2 were downregulated in the siRNA-treated cells. Furthermore, we observed that the mRNA levels of HRAS, KRAS, NRAS, and MRAS decreased upon IQGAP1 silencing. These findings indicate that IQGAP1 potentially regulates the expression of IQGAP and RAS gene families and demonstrate its regulatory role in the apoptotic network. Taken together, our findings suggest that IQGAP1 silencing plays crucial roles in the apoptosis of HepG2 cells and lowers their proliferative and invasive capacities.

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Acknowledgments

The project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH) King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia, award number 12-BIO2926-02.

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Authors and Affiliations

  1. Pharmacology and Toxicology Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Khairy MA Zoheir, Sheikh Fayaz Ahmad & Mushtaq Ahmad Ansari

  2. Cell Biology Department, National Research Centre, Cairo, 12622, Egypt

    Khairy MA Zoheir

  3. Hormones Department, Medical Research Division, National Research Centre, Cairo, 12622, Egypt

    Ahmed A. Abd-Rabou

  4. Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia

    Gamaleldin I Harisa

  5. Vitiligo Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Ashok Kumar

  6. Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt

    Adel R Abd-Allah

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  1. Khairy MA Zoheir
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Correspondence to Khairy MA Zoheir.

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Zoheir, K.M., Abd-Rabou, A.A., Harisa, G.I. et al. IQGAP1 gene silencing induces apoptosis and decreases the invasive capacity of human hepatocellular carcinoma cells. Tumor Biol. 37, 13927–13939 (2016). https://doi.org/10.1007/s13277-016-5283-8

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  • DOI: https://doi.org/10.1007/s13277-016-5283-8

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