Pseudogene KRT17P3 Promotes NSCLC Progression Through Mir-338-3p/USP7/C-Myc

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Non-small cell lung cancer (NSCLC) is a major cause of cancer mortality.
• The molecular drivers of NSCLC remain incompletely understood.
• The pseudogene KRT17P3 is implicated in NSCLC chemoresistance but its role in tumorigenesis is unclear.

Purpose of the Study:

• To investigate the functional role of KRT17P3 in non-small cell lung cancer (NSCLC) development.
• To elucidate the molecular mechanisms by which KRT17P3 influences NSCLC progression.
• To evaluate KRT17P3 as a potential prognostic biomarker and therapeutic target for NSCLC.

Main Methods:

• In vitro assays assessed KRT17P3's impact on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
• In vivo experiments evaluated KRT17P3's role in tumor metastasis.
• Mechanistic studies included bioinformatics, RNA immunoprecipitation (RIP), luciferase, and chromatin immunoprecipitation (ChIP) assays.

Main Results:

• KRT17P3 significantly promotes NSCLC cell proliferation, migration, invasion, and EMT, and enhances tumor metastasis.
• KRT17P3 stabilizes the oncogenic protein c-Myc by competitively binding miR-338-3p, upregulating deubiquitinase USP7.
• KRT17P3 expression is upregulated by FOXA1-mediated promoter activation, driving NSCLC tumorigenesis.

Conclusions:

• KRT17P3 is a critical driver of NSCLC progression.
• KRT17P3 regulates the USP7/c-Myc axis through miR-338-3p, impacting tumorigenesis.
• KRT17P3 holds potential as a prognostic biomarker and therapeutic target for NSCLC.