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CRISPR/Cas9-mediated silencing of CD44: unveiling the role of hyaluronic acid-mediated interactions in cancer drug resistance

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Abstract

A comprehensive overview of CD44 (CD44 Molecule (Indian Blood Group)), a cell surface glycoprotein, and its interaction with hyaluronic acid (HA) in drug resistance mechanisms across various types of cancer is provided, where CRISPR/Cas9 gene editing was utilized to silence CD44 expression and examine its impact on cancer cell behavior, migration, invasion, proliferation, and drug sensitivity. The significance of the HA-CD44 axis in tumor microenvironment (TME) delivery and its implications in specific cancer types, the influence of CD44 variants and the KHDRBS3 (KH RNA Binding Domain Containing, Signal Transduction Associated 3) gene on cancer progression and drug resistance, and the potential of targeting HA-mediated pathways using CRISPR/Cas9 gene editing technology to overcome drug resistance in cancer were also highlighted.

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Fig. 1

Adapted from Szatanek R, Baj-Krzyworzeka M. CD44 and Tumor-Derived Extracellular Vesicles (TEVs). Possible Gateway to Cancer Metastasis. International Journal of Molecular Sciences. 22(3), 1463 (2021))

Fig. 2

Adapted from Wang, M., Chen, M., Wu, X. et al. CRISPR applications in cancer diagnosis and treatment. Cell Mol Biol Lett 28, 73 (2023))

Fig. 3

Adapted from Sharma, U., Murmu, M., Barwal, T.S. et al. A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/β-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response. Curr. Oncol. 29, 2326-2349 (2022))

Fig. 4

Adapted from Sarrand J, Soyfoo MS. Involvement of Epithelial-Mesenchymal Transition (EMT) in Autoimmune Diseases. International Journal of Molecular Sciences. 24(19), 14481(2023))

Fig. 5

Adapted from Sharma, U., Murmu, M., Barwal, T.S. et al. A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/β-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response. Curr. Oncol. 29, 2326-2349 (2022))

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Data availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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    Zhujun Xu

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Xu, Z. CRISPR/Cas9-mediated silencing of CD44: unveiling the role of hyaluronic acid-mediated interactions in cancer drug resistance. Naunyn-Schmiedeberg's Arch Pharmacol 397, 2849–2876 (2024). https://doi.org/10.1007/s00210-023-02840-8

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