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

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Cross-downregulation of CDK6-PI3K axis in the cdk6-deficient KB-C2 cells reduced the expression of ABCB1 by inducing responsive alternative splicing (AS) in the pre-mRNA of ABCB1. A Relative expression of the functional proteins including CDK6, CDK4, ABCB1, PIK3CA and PIK3CB in KB-C2 and the cdk6-deficient KB-C2 cell populations. Major transcripts according to each intact protein were calculated in the cells expressing identical level of GAPDH. B Heatmap showed that through AS of pre-mRNA in response to cdk6 deletion, the level of the transcripts expressing functional ABCB1 protein was significantly downregulated whereas some transcripts expressing truncated inactive ABCB1 peptides (e.g., ENST00000488737) were upregulated in the KB-C2 cells with deleted cdk6 gene. C Differential expression heatmap showing downregulation of PI3K 110α and 110β (encoded by PIK3CA and PIK3CB genes, respectively) in the KB-C2-k.o.cdk6 population as compared with the non-gene deficient KB-C2 cells. D Protein-protein interaction network showing the pathways linking the differently expressed proteins in the KB-C2 cells with deficiency of cdk6. This network reflects the factors that have most intimate relationships with CDK6, and the pathways that are regulated by deletion of cdk6 and belong to different biological functions. Yellow represents the protein with no significant difference in expression. From green to blue, the downregulation of proteins is gradually obvious. From orange to red, the up regulation of proteins is gradually obvious