Identifying global expression patterns and key regulators in epithelial to mesenchymal transition through multi-study...

Area of Science:

• Cancer Biology
• Molecular Oncology
• Genomics

Background:

• Epithelial to mesenchymal transition (EMT) is crucial for development, wound healing, and tumor metastasis.
• EMT involves epithelial cells gaining motility and invasive properties, contributing to cancer progression.

Purpose of the Study:

• To identify novel genes and global expression patterns associated with EMT.
• To validate candidate EMT regulators in cancer cell models.

Main Methods:

• Integrated 15 gene expression microarray datasets from GEO, encompassing 6 cancer types.
• Applied normalization and correction methods to identify a consensus list of differentially expressed EMT genes.
• Validated novel EMT genes, including C1orf116, at mRNA and protein levels using in vitro models and siRNA knockdown.

Main Results:

• Identified known epithelial (CDH1) and mesenchymal (ZEB1) markers, alongside novel epithelial (LSR, S100A14) and mesenchymal (DPYSL3) genes.
• Discovered C1orf116 as a novel EMT-associated gene, with decreased expression linked to poor prognosis in lung and prostate cancer.
• Demonstrated that C1orf116 knockdown in prostate cancer cells induced mesenchymal gene expression, suggesting a role in maintaining epithelial phenotype.

Conclusions:

• A comprehensive analysis identified global EMT expression patterns and novel regulatory genes.
• C1orf116 is a novel candidate driver of the epithelial phenotype and a potential prognostic marker in cancer.