CircFAT1 Promotes Lung Adenocarcinoma Progression by Sequestering miR-7 from Repressing IRS2-ERK-mediated CCND1...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Targeted therapies for lung cancer rely on understanding coding gene functions.
• Noncoding RNAs, particularly circular RNAs (circRNAs), are increasingly recognized for their roles in cancer development.
• Investigating circRNA functions and regulatory pathways is key to developing new cancer diagnostics and therapeutics.

Purpose of the Study:

• To elucidate the role of circFAT1 in lung adenocarcinoma (LUAD) progression.
• To explore the potential of circFAT1 as a therapeutic target in LUAD.
• To understand the molecular mechanisms by which circFAT1 influences LUAD.

Main Methods:

• CircRNA sequencing (circRNA-seq) was performed on A549 cells.
• Gain-of-function and loss-of-function cellular assays were conducted on A549 and PC9 LUAD cell lines.
• In vitro and in vivo experiments, including xenograft models, were utilized to assess proliferation and treatment response.

Main Results:

• circFAT1 was identified as a highly expressed circRNA and was significantly upregulated in human LUAD tissues.
• circFAT1 promoted LUAD cell proliferation both in vitro and in vivo.
• Molecular analysis revealed circFAT1 sequesters miR-7, upregulating IRS2 and downstream signaling (ERK1/2 phosphorylation, CCND1 expression), thereby promoting tumor progression.
• Knockdown of circFAT1 enhanced the efficacy of DDP treatment in LUAD cells and xenograft models.

Conclusions:

• circFAT1 promotes LUAD tumorigenesis by sequestering miR-7, leading to IRS2-ERK1/2-mediated CCND1 expression.
• circFAT1 represents a potential therapeutic target for LUAD.
• circFAT1 may serve as an important biomarker for precision treatment in LUAD patients.