Splicing Machinery Is Impaired in Oral Squamous Cell Carcinomas and Linked to Key Pathophysiological Features

Area of Science:

• Molecular Oncology
• Cancer Genomics
• Biochemistry

Background:

• Alternative splicing dysregulation is recognized as a hallmark of cancer.
• Splicing machinery (SM) components are potential targets for cancer therapy.
• Oral squamous cell carcinoma (OSCC) is a prevalent head and neck cancer with unmet therapeutic needs.

Purpose of the Study:

• To characterize the expression of splicing machinery (SM) components in OSCC.
• To investigate the association between SM component expression and clinical/histopathological features.
• To evaluate the therapeutic potential of SM inhibition in OSCC.

Main Methods:

• Prospective case-control study analyzing 59 SM components in 37 OSCC patients' tumor and healthy tissues.
• Correlation analysis of SM component expression with clinical and histopathological data.
• In vitro evaluation of pladienolide-B (SM inhibitor) on OSCC cell proliferation.

Main Results:

• Significant dysregulation of 12 out of 59 (20%) SM components was observed in OSCC compared to adjacent healthy tissues.
• Altered SM component expression correlated with less aggressive clinical features and improved overall survival.
• Pladienolide-B treatment markedly reduced the proliferation rate of primary OSCC cell cultures.

Conclusions:

• Splicing machinery dysregulation is a significant feature of OSCC, linked to disease characteristics and patient outcomes.
• Inhibition of splicing machinery activity, demonstrated by pladienolide-B, exhibits direct anti-proliferative effects on OSCC cells.
• Targeting the splicing machinery represents a promising therapeutic strategy for oral squamous cell carcinoma.