CircRAPGEF5 Promotes LUAD by Mediating the HOXC6 Stability

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Lung adenocarcinoma (LUAD) is a leading cause of cancer death, often diagnosed at advanced stages with poor prognosis.
• The specific molecular mechanisms driving LUAD progression, particularly involving HOXC6, remain incompletely understood.

Purpose of the Study:

• To elucidate the role and molecular mechanisms of HOXC6 in lung adenocarcinoma (LUAD) progression.
• To investigate the regulatory network involving circRAPGEF5, HOXC6, and HOXB2 in LUAD.

Main Methods:

• Quantitative reverse transcription PCR (RT-qPCR), immunohistochemistry (IHC), Western blot, immunofluorescence (IF), CCK-8, scratch, and Transwell assays were used to assess gene/protein expression and cell behavior.
• Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were employed to explore molecular interactions.
• In vivo xenograft and metastatic mouse models, along with fluorescence in situ hybridization (FISH), were utilized to evaluate tumor growth and metastasis.

Main Results:

• Knockdown of circRAPGEF5 significantly inhibited LUAD cell proliferation, migration, invasion, tumor growth, and metastasis in vivo.
• circRAPGEF5 enhances HOXC6 mRNA stability by interacting with HNRNPC, leading to increased HOXC6 expression.
• HOXC6 transcriptionally activates HOXB2, and HOXC6 overexpression can reverse the inhibitory effects of circRAPGEF5 knockdown.

Conclusions:

• circRAPGEF5 promotes LUAD progression and metastasis by stabilizing HOXC6 mRNA via HNRNPC and subsequently activating HOXB2 transcription.
• Targeting the circRAPGEF5/HOXC6/HOXB2 axis presents a potential therapeutic strategy for lung adenocarcinoma.