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

• Published in: International journal of molecular sciences 2024-06, Vol.25 (13), p.6929
• Main Authors: Sanjuan-Sanjuan, Alba, Alors-Perez, Emilia, Sanchez-Frías, Marina, Monserrat-Barbudo, José A, Falguera Uceda, Mabel, Heredero-Jung, Susana, Luque, Raúl M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alternative Splicing; Apoptosis; Biomarkers; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Case-Control Studies; Cell cycle; Cell Line, Tumor; Cell Proliferation; Epoxy Compounds - pharmacology; Female; Gene Expression Regulation, Neoplastic; head and neck; Human papillomavirus; Humans; Macrolides - pharmacology; Male; Medical prognosis; Metastasis; Middle Aged; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Mutation; Oral cancer; Prospective Studies; RNA Splicing; splicing; Squamous cell carcinoma; therapeutic tool
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25136929

Alternative splicing dysregulation is an emerging cancer hallmark, potentially serving as a source of novel diagnostic, prognostic, or therapeutic tools. Inhibitors of the activity of the splicing machinery can exert antitumoral effects in cancer cells. We aimed to characterize the splicing machinery (SM) components in oral squamous cell carcinoma (OSCC) and to evaluate the direct impact of the inhibition of SM-activity on OSCC-cells. The expression of 59 SM-components was assessed using a prospective case-control study of tumor and healthy samples from 37 OSCC patients, and the relationship with clinical and histopathological features was assessed. The direct effect of pladienolide-B (SM-inhibitor) on the proliferation rate of primary OSCC cell cultures was evaluated. A significant dysregulation in several SM components was found in OSCC vs. adjacent-healthy tissues [i.e., 12 out of 59 (20%)], and their expression was associated with clinical and histopathological features of less aggressiveness and overall survival. Pladienolide-B treatment significantly decreased OSCC-cell proliferation. Our data reveal a significantly altered expression of several SM-components and link it to pathophysiological features, reinforcing a potential clinical and pathophysiological relevance of the SM dysregulation in OSCC. The inhibition of SM-activity might be a therapeutic avenue in OSCC, offering a clinically relevant opportunity to be explored.