The landscape of long noncoding RNA during cutaneous squamous cell carcinoma progression

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Cutaneous squamous cell carcinoma (cSCC) is a prevalent cancer with significant morbidity, especially in its metastatic form.
• The progression from pre-malignant Actinic Keratosis (AK) to invasive and metastatic cSCC involves poorly defined molecular mediators.
• Long non-coding RNAs (lncRNAs) are emerging as critical, yet understudied, players in cSCC pathogenesis.

Purpose of the Study:

• To comprehensively map the landscape of lncRNA expression across the cSCC disease continuum.
• To identify functional lncRNA drivers implicated in cSCC progression.
• To develop and validate a prognostic lncRNA signature.

Main Methods:

• Analysis of bulk RNA sequencing data from 110 patient samples spanning normal skin, AK, primary cSCC, and metastases.
• Development of a bioinformatics pipeline for lncRNA function inference via co-expression patterns.
• In vitro knockdown experiments to investigate the functional role of LINC00941.

Main Results:

• lncRNA expression profiles accurately distinguish disease states and progression along the cSCC continuum.
• A 267-lncRNA signature was developed, correlating with a progenitor-like state and predicting poor prognosis in head and neck squamous cell carcinoma (HNSC) and pancreatic adenocarcinoma (PAAD).
• Knockdown of LINC00941 demonstrated its necessity for cell proliferation and colony formation in vitro.

Conclusions:

• This study provides a detailed transcriptomic map of lncRNAs in cSCC, highlighting their functional significance.
• lncRNAs serve as potential biomarkers and drivers of disease progression in cSCC.
• The findings suggest lncRNAs may also play roles in other cancer types.