title: IQGAP1 gene silencing induces apoptosis and decreases the invasive capacity of human hepatocellular carcinoma cells.
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.
authors.affiliation: Pharmacology and Toxicology Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. khma25@gmail.com.|Cell Biology Department, National Research Centre, Cairo, 12622, Egypt. khma25@gmail.com.
authors.forename: Khairy Ma
authors.initials: KM
authors.lastname: Zoheir
authors.affiliation: Hormones Department, Medical Research Division, National Research Centre, Cairo, 12622, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Abd-Rabou
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
authors.forename: Gamaleldin I
authors.initials: GI
authors.lastname: Harisa
authors.affiliation: Vitiligo Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Pharmacology and Toxicology Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Sheikh Fayaz
authors.initials: SF
authors.lastname: Ahmad
authors.affiliation: Pharmacology and Toxicology Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mushtaq Ahmad
authors.initials: MA
authors.lastname: Ansari
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Adel R
authors.initials: AR
authors.lastname: Abd-Allah
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D020703:ras GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C101203:IQ motif containing GTPase activating protein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020703:ras GTPase-Activating Proteins
keywords: Apoptosis; HepG2 cells; IQGAP1; RAS; siRNA