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The WEE1 mRNA 3' untranslated region (3' UTR) is a critical regulatory segment of the messenger RNA encoding the WEE1 G2 checkpoint kinase (UniProt P30291). WEE1 is a nuclear kinase that negatively regulates the G2/M transition by phosphorylating and inactivating the CDK1/Cyclin B complex. The 3' UTR serves as a hub for post-transcriptional control, containing conserved binding sites for various microRNAs (miRNAs) such as miR-128, miR-155, and miR-424 (Wu et al., 2021). In many cancers, the loss of these regulatory miRNAs leads to the overexpression of WEE1, which provides a survival advantage by allowing cells to repair DNA damage before entering mitosis (Matthews et al., 2022). This overexpression is associated with poor prognosis and resistance to conventional chemotherapy and radiotherapy. Therapeutic strategies targeting the WEE1 mRNA 3' UTR involve the use of miRNA mimics or antisense oligonucleotides to reduce WEE1 protein levels, thereby inducing mitotic catastrophe in cancer cells (Cai et al., 2017). This approach is particularly effective in p53-deficient tumors that rely heavily on the G2 checkpoint for survival.
Binding of microRNAs or antisense agents to the 3' UTR induces mRNA degradation or inhibits translation, thereby reducing WEE1 protein levels and promoting cell cycle arrest or apoptosis (Cai et al., 2017).
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