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Updated: Jun 21, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

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

Alba Sanjuan-Sanjuan1,2,3,4, Emilia Alors-Perez1,2,5,6, Marina Sanchez-Frías1,2,7

  • 1Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain.

International Journal of Molecular Sciences
|July 13, 2024
PubMed

Insights

Alternative splicing machinery (SM) is dysregulated in oral squamous cell carcinoma (OSCC). Inhibiting SM activity with pladienolide-B reduced OSCC cell proliferation, suggesting a potential new therapy for this cancer.

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.
Keywords:
alternative splicingbiomarkersdiagnosticgenetic alterationshead and neckoral cancersplicingtherapeutic tool

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