Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy
OSCC is a common cancer of the head and neck. Despite ongoing efforts, there remains a dearth of targeted drugs capable of effectively inhibiting OSCC growth. As the earliest discovered proto-oncogene in the SRSF family, targeted inhibition of SRSF1 plays an important role in tumor suppression. However, a comprehensive report on the expression, function, and mechanism of SRSF1 in OSCC has yet to be presented. This study retrospectively analyzed clinical samples from OSCC patients and discovered a significant correlation between the SRSF1 expression level and poor prognosis. In vitro experimentation demonstrated that SRSF1 knockdown inhibited OSCC growth, survival, lysosomal biogenesis and autophagy. To confirm the significance of lysosomal function and autophagy in the regulation of OSCC growth by SRSF1, cell rescue models were constructed. The aforementioned findings were subsequently validated in xenograft models. Ultimately, targeted knockdown of SRSF1 was found to significantly suppress OSCC growth by impeding lysosomal biogenesis and autophagy. Overall design: RNA-sequencing of the stable si-NC and si-SRSF1 groups of SCC-4 and CAL-27 cells was carried out by GeneChem. The mRNA samples were collected, processed, and prepared for library creation following the producer's guidelines. In summary, total mRNA was obtained, and the Qubit® RNA Assay Kit in a Qubit® 2.0 fluorometer was utilized to determine the RNA concentration. Subsequently, NEBNext® UltraTM RNA Library Prep Kit for Illumina® was employed to produce sequence libraries following the manufacturer's recommendations. DESeq2 R package (1.16.1) was used to analyze the expression differences between si-NC and si-SRSF1 cells. The threshold levels were log2 (fold change) >1.5 and q<0.05.