Fig. 9

CD44 affects the biological behavior of PC through regulation of the endoplasmic reticulum degradation pathway. A GSEA of differentially expressed genes indicated that when CD44 was inhibited, the ERAD pathway was downregulated. B Heatmap showed differential genes enriched in ERAD signal pathway after silencing CD44. C ERS-related protein GRP78, IRE1a/p-IRE1a, TRAF2, ASK1/p-ASK1, JNK/p-JNK, BCL-2 were detected by Western-blot. D Schematic diagram of the proposed role of CELF2 in PC and its mechanism. ALKBH5-mediated m6A methylation unstabilizes and downregulates CELF2. CELF2 exerts oncogenic effect in PC by regulating CD44 alternative splicing to hinder CD44s switching towards CD44v, further inhibits p-IRE1a on the ER surface to form a dimer with TRAF2 to hinder the initiation of the mitochondrial apoptotic pathway, thus contributing to tumor progression of PC. Data are shown as the mean ± SD of three replicates. *P < 0.05, **P < 0.01