Cell Biology Department, Biotechnology Research Institute, National Research Centre, 33 Bohouth St., 12622, Dokki, Cairo, Egypt.
Pharmacognosy Department, National Research Centre, El-Behooth St., 12622 Dokki, Cairo, Egypt.
Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2387-2395. doi: 10.31557/APJCP.2022.23.7.2387.
Colorectal carcinoma (CRC) represents life-threatening problems worldwide. IQ motif containing GTPase activating protein 1 (IQGAP1) is acting as oncogenesis regulators. RNAi is proposed as promising cancer therapeutics.
The objective of this work to explore the consequences of the IQGAP1 silence as a goal for treating CRC using the HCT166 cells as a model for human colon cancer.
RNAi technology was used to design a short specific sequence of RNA (shRNA) to silence the IQGAP1 oncogene. The impact of IQGAP1 silencing on IQGAPs, Ras, IL-8, and TRAIL was investigated. Furthermore, the effect of IQGAP1 silencing on cell viability, proliferation, apoptosis, and invasive capacity was investigated.
The present results revealed that IQGAP1 shRNA-treated HCT166 cells showed no invasive capacity compared to the control cells. The silencing of IQGAP1 induced remarkable downregulation of IQGAP1, RAS (H&K), IL-8, CXCR1, CXCR2, NF-kB, BCL-2, and apoptosis of HCT166 cells. On the contrary, IQGAP2, IQGAP3, DR4, DR5, CASP-3, and BAX genes were significantly up-regulated.
The IQGAP1 regulates the expression of IQGAPs, Ras, IL-8 receptors, and the apoptotic network. Therefore, the silence of IQGAP1 is a promising strategy for colon cancer therapy.
结直肠癌（CRC）是全球范围内危及生命的问题。IQ motif containing GTPase activating protein 1（IQGAP1）作为致癌调节因子发挥作用。RNAi 被提议作为有前途的癌症治疗方法。
本研究旨在探讨使用 HCT166 细胞作为人类结肠癌模型，通过沉默 IQGAP1 来治疗 CRC 的可能性。
使用 RNAi 技术设计了一个短的特定 RNA（shRNA）序列来沉默 IQGAP1 致癌基因。研究了 IQGAP1 沉默对 IQGAPs、Ras、IL-8 和 TRAIL 的影响。此外，还研究了 IQGAP1 沉默对细胞活力、增殖、凋亡和侵袭能力的影响。
本研究结果表明，与对照细胞相比，IQGAP1 shRNA 处理的 HCT166 细胞没有侵袭能力。IQGAP1 的沉默诱导了 IQGAP1、RAS（H&K）、IL-8、CXCR1、CXCR2、NF-kB、BCL-2 和 HCT166 细胞凋亡的显著下调。相反，IQGAP2、IQGAP3、DR4、DR5、CASP-3 和 BAX 基因显著上调。
IQGAP1 调节 IQGAPs、Ras、IL-8 受体和凋亡网络的表达。因此，沉默 IQGAP1 是一种有前途的结肠癌治疗策略。
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