Fig. 6

Inhibition of CDK12/13 impairs splicing and expression of cancer-relevant genes in HGSOC. a Gene Ontology analyses of the biological processes significantly affected by up-regulated IR and ALE events in HGSOC cells. b KEGG pathway analysis of the genes significantly affected by up-regulated IR and ALE events in HGSOC cells. c, f, i, Profiles of the RNA-seq reads of the IR events in PAX8 (c), EGFR (f), ATRIP (i) genes in OVCAR3 cells treated with DMSO (upper graph) or THZ531 (lower graph). Sequence reads (vertical gray lines), exons (grey boxes), and introns (horizontal lines and red boxes) are shown. d, g, j, Schematic representation for each event analysed (top panels): black arrows in the scheme indicate primers used for the PCR analysis. Bar graphs (bottom panels) show the results of qPCR analyses for the expression of the retained intron (red boxes) relative to L34 (Data represent mean ± SD of three biological replicates; ∗ P ≤ 0.05, **P ≤ 0.01; t-test). e, h, k Western blot analyses of the expression of PAX8 (e), EGFR (h), ATRIP (k) proteins in PDO cell extracts. HSP90 was included as a loading control