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利用 IQGAP1 的 shRNA 进行结肠癌治疗的新方法：以 HCT116 为替代模型的结直肠癌细胞癌。

Novel Approach Using shRNA of IQGAP1 for Colon Cancer Therapy: HCT116 as a Surrogate Model Colorectal Carcinoma.

机构信息

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.

出版信息

Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2387-2395. doi: 10.31557/APJCP.2022.23.7.2387.

DOI:10.31557/APJCP.2022.23.7.2387
PMID:35901346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9727335/
Abstract

BACKGROUND

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.

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

目的

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6031/9727335/d32f6e8a42a2/APJCP-23-2387-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6031/9727335/1124d46efe5c/APJCP-23-2387-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6031/9727335/ffeb7ccd7bf6/APJCP-23-2387-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6031/9727335/d32f6e8a42a2/APJCP-23-2387-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6031/9727335/1124d46efe5c/APJCP-23-2387-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6031/9727335/ffeb7ccd7bf6/APJCP-23-2387-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6031/9727335/d32f6e8a42a2/APJCP-23-2387-g004.jpg

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The Significance of Epithelial-to-Mesenchymal Transition for Circulating Tumor Cells.上皮-间质转化对循环肿瘤细胞的意义
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Coexpression of IQ-domain GTPase-activating protein 1 (IQGAP1) and Dishevelled (Dvl) is correlated with poor prognosis in non-small cell lung cancer.IQ结构域GTP酶激活蛋白1（IQGAP1）与蓬乱蛋白（Dvl）的共表达与非小细胞肺癌的不良预后相关。
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