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Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect
Chou-Yi Hsu1, Abdulsalam Najm Mohammed2, Ahmed Hjazi3
1Thunderbird School of Global Management, Arizona State University, Tempe Campus, Phoenix, AZ, 85004, USA. t545316@gmail.com.
Abstract:
Enhancer of zeste homolog 2 (EZH2) serves as the enzymatic catalytic subunit of the polycomb repressive complex 2 (PRC2), which is capable of modifying the expression of downstream target genes through the trimethylation of Lys-27 on histone 3 (H3K27me3). In addition to its role in H3K27me3 modification, EZH2 may influence gene expression through alternative mechanisms. The involvement of EZH2 in cellular processes such as proliferation, apoptosis, and senescence has been established. Its significant contributions to the pathophysiology of cancer have garnered considerable attention. Consequently, pursuing EZH2 as a target for cancer therapy has become a prominent area of research, leading to the development of various EZH2 inhibitors. A growing number of efforts are being made to investigate the possible application of small interfering RNA (siRNA) in medical applications after the practical application of this technique to decrease gene expression in various research models. Pharmacological inhibition of EZH2 induces apoptosis in cancer cells, while siRNA-mediated downregulation of EZH2 suppresses cancer cell growth. The cell cycle is modulated by siRNA-induced suppression of EZH2, yet its precise cause is unclear. Furthermore, inadequate research has been done on the signaling route affecting cancer cells' cell cycle following EZH2 suppression with siRNA. Investigating the molecular basis of EZH2 siRNA's anticancer activity will aid in developing fresh methods for identifying, managing, and preventing cancer.
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