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. 2022 Apr 22;21:103. doi: 10.1186/s12943-022-01524-w

Fig. 5.

Fig. 5

Regulation of CDK6-PI3K axis on ABCB1-mediated drug resistance. Knockout of cdk6 gene in KB-C2 with CRISPR/Cas9 technique induced attenuation of ABCB1-mediated drug resistance. It promoted AS in the pre-mRNA expressing ABCB1, generating differential expression of the transcripts encoding functional ABCB1 protein or truncated abnormal peptides, further decreased the level of functional ABCB1 transporters. With the deficiency of cdk6 in KB-C2 cells, PI3K 110α and 110β expression were downregulated, which induced AS of ABCB1 pre-mRNA and led to inhibition of ABCB1 expression and reversal of ABCB1-mediated MDR, inhibiting cell division and promoting cell apoptosis. A series of signaling pathways critical for malignancies were downregulated in the KB-C2-k.o.cdk6 cell population