Oncogenic Peptide Encoded by Noncoding RNA of FOXM1 Promotes Pancreatic Cancer Malignancy Through PI3K/AKT Signaling

Area of Science:

• Molecular Biology
• Oncology
• RNA Biology

Background:

• Alternative splicing of FOXM1 generates diverse isoforms with complex functions.
• One such isoform, FOXM1s, is a short noncoding RNA with an identified encoded peptide.

Purpose of the Study:

• To investigate the function and mechanism of the FOXM1s-encoded peptide in pancreatic cancer development and progression.
• To determine if FOXM1s can serve as a therapeutic target for pancreatic ductal adenocarcinoma (PDAC).

Main Methods:

• RT-PCR to analyze FOXM1s expression in pancreatic cancer tissues and cell lines.
• Immunofluorescence (IF) and bioinformatics to correlate gene expression with clinicopathologic characteristics.
• In vitro assays and mouse models to evaluate effects on proliferation, migration, invasion, and stemness.
• Overexpression and knockdown approaches to validate functional roles.
• Western blotting and specific antibody use to confirm FOXM1s peptide expression and PI3K/AKT pathway activation.

Main Results:

• FOXM1s expression was significantly increased in human pancreatic cancer tissues and cell lines.
• Overexpression of FOXM1s promoted pancreatic cancer progression, while mutation attenuated its effect, suggesting peptide-mediated function.
• FOXM1s significantly enhanced cell proliferation, migration, invasion, liver metastasis, and stemness gene expression.
• Mechanistically, the FOXM1s peptide activated the PI3K/AKT signaling pathway.

Conclusions:

• FOXM1s encodes a peptide that exhibits oncogenic function in pancreatic cancer progression.
• Activation of the PI3K/AKT signaling pathway is a key mechanism by which FOXM1s exerts its effects.
• FOXM1s represents a novel molecular target for pancreatic cancer therapy.