Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy

Abstract

Summary: Oral squamous cell carcinoma (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 serine/arginine-rich splicing factor 1 (SRSF1) plays an important role in tumor suppression. However, the expression, function, and mechanism of SRSF1 in OSCC have not been comprehensively reported. 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.

Keywords

• Drugs
• Molecular biology
• Cancer