Mechanism of the engineered sgRNA action to counter VCR resistance (IMAGE)
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Vincristine monotherapy triggers NF-κB activation, inducing OIP5 expression linked to cancer cell resistance against vincristine. The engineered sgRNA, housing the NF-κB aptamer, competitively binds with NF-κB, leading to a conformational change from inactive state to active state that frees sgRNA's guide region. This guides NF-κB to downregulate OIP5 expression and concurrently obstructs NF-κB-mediated drug resistance pathways. Ultimately, this dual action reverses VCR resistance in bladder cancer cells. Diagram by Binbin Zheng.
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