Int J Biol Sci 2019; 15(6):1177-1186. doi:10.7150/ijbs.33103
PCBP1 inhibits the expression of oncogenic STAT3 isoform by targeting alternative splicing of STAT3 exon 23
1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, PR China.
2. Department of Endodontics, School & Hospital of Stomatology, Wuhan University, Wuhan, PR China.
*These authors contributed equally to this work.
Wang X, Guo J, Che X, Jia R. PCBP1 inhibits the expression of oncogenic STAT3 isoform by targeting alternative splicing of STAT3 exon 23. Int J Biol Sci 2019; 15(6):1177-1186. doi:10.7150/ijbs.33103. Available from http://www.ijbs.com/v15p1177.htm
STAT3 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 STAT3 in the clinic. STAT3 has two isoforms generated by alternative splicing of exon 23. STAT3α is the longer isoform and encodes the full-length oncogenic STAT3α protein. STAT3β is shorter and encodes the truncated and tumor-suppressive STAT3β protein. It remains unknown how the alternative splicing of STAT3 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 STAT3α /STAT3β isoforms and the expression of STAT3α protein. Moreover, increased PCBP1 inhibited the growth of oral squamous cell carcinoma and breast cancer cells, and the expression of STAT3 target genes. Our results demonstrated that PCBP1 is the key splicing factor that promotes the switch from oncogenic isoform STAT3α to tumor-suppressive isoform STAT3β. Our results pave the way for finding new anti-STAT3 methods for cancer treatment.
Keywords: STAT3, Alternative splicing, Oncogene, head and neck cancer, PCBP1