Our investigation revealed a multitude of aberrant alternative splicing events within head and neck tumor tissues, most notably the pronounced skipping of exon 7 in the SLC37A4 gene. This splicing anomaly leads to the production of a truncated isoform, SLC37A4-S, which is associated with a poor prognosis and significantly augments the proliferation and metastatic potential of oral cancer cells relative to the wild-type isoform, SLC37A4-L. Mechanically, SRSF9 may play a regulatory role in the aberrant splicing of SLC37A4. Furthermore, SRSF9 is capable of undergoing LLPS, a process driven by its arginine-serine-rich (RS) domain. Disruption of SRSF9 LLPS through the use of inhibitors or mutants effectively prevents its regulatory influence on the splicing of SLC37A4. Significantly, our research demonstrates that both SRSF9 and its regulated splicing isoforms of SLC37A4-S contribute to cisplatin chemotherapy resistance in oral cancer cells.

Our investigation revealed a multitude of aberrant alternative splicing events within head and neck tumor tissues, most notably the pronounced skipping of exon 7 in the SLC37A4 gene. This splicing anomaly leads to the production of a truncated isoform, SLC37A4-S, which is associated with a poor prognosis and significantly augments the proliferation and metastatic potential of oral cancer cells relative to the wild-type isoform, SLC37A4-L. Mechanically, SRSF9 may play a regulatory role in the aberrant splicing of SLC37A4. Furthermore, SRSF9 is capable of undergoing LLPS, a process driven by its arginine-serine-rich (RS) domain. Disruption of SRSF9 LLPS through the use of inhibitors or mutants effectively prevents its regulatory influence on the splicing of SLC37A4. Significantly, our research demonstrates that both SRSF9 and its regulated splicing isoforms of SLC37A4-S contribute to cisplatin chemotherapy resistance in oral cancer cells.