PCBP1 inhibits the expression of oncogenic STAT3 isoform by targeting alternative splicing of STAT3 exon 23.

plays very important roles in the initiation and development of tumors. Despite of extensive studies in repressing its activation and function via multiple ways, so far, there are few effective therapeutic methods to inhibit duanyu18133 in the clinic. duanyu18133 has two isoforms generated by alternative splicing of exon 23. is the longer isoform and encodes the full-length oncogenic duanyu18133α protein. is shorter and encodes the truncated and tumor-suppressive duanyu18133β protein. It remains unknown how the alternative splicing of duanyu18133 exon 23 is regulated. Here, we discovered that there is an exonic splicing suppressor (ESS) in exon 23. Importantly, splicing factor PCBP1 binds to this ESS. Overexpression of PCBP1 significantly reduced the proportion of duanyu18133α isoforms and the expression of duanyu18133α protein. Moreover, increased PCBP1 inhibited the growth of oral squamous cell carcinoma and breast cancer cells, and the expression of duanyu18133 target genes. Our results demonstrated that PCBP1 is the key splicing factor that promotes the switch from oncogenic isoform duanyu18133α to tumor-suppressive isoform Our results pave the way for finding new methods for cancer treatment.

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