Satellite double-stranded RNA induces mesenchymal transition in pancreatic cancer by regulating alternative splicing

Area of Science:

• Molecular Biology
• Cancer Research
• Genomics

Background:

• Human satellite II (HSATII) is a repetitive DNA sequence found in pericentromeric regions.
• Aberrant HSATII transcription occurs in epithelial cancers, including pancreatic cancer.
• The role of double-stranded RNAs (dsRNAs) in cancer progression, whether tumor-promoting or suppressing, is debated.

Purpose of the Study:

• To investigate the molecular function of double-stranded HSATII (dsHSATII) RNA in cancer.
• To explore the role of dsHSATII in epithelial-mesenchymal transition (EMT) and cell invasiveness in pancreatic cancer.

Main Methods:

• Overexpression of dsHSATII in pancreatic cancer cells.
• Identification and characterization of RNA-binding proteins interacting with dsHSATII.
• Assessment of cell morphology, invasiveness, and gene alternative splicing.
• Manipulation of spermatid perinuclear RNA-binding protein (STRBP) levels.

Main Results:

• Overexpression of dsHSATII induced mesenchymal-like morphology and enhanced invasiveness of pancreatic cancer cells.
• Spermatid perinuclear RNA-binding protein (STRBP) was identified as a dsHSATII-binding protein.
• STRBP overexpression rescued the dsHSATII-induced mesenchymal transition.
• STRBP regulates alternative splicing of EMT-associated genes, including CLSTN1, influencing EMT-like changes.

Conclusions:

• dsHSATII RNA possesses a tumor-promoting function by inducing EMT-like changes and enhancing pancreatic cancer cell invasiveness.
• STRBP acts as a key regulator in the dsHSATII-mediated EMT pathway.
• These findings elucidate the significance of aberrant satellite array expression in malignant tumors.