hsa_circ_0005963 downregulation suppresses NSCLC malignant progression by miR-506-3p/SOX9-mediated stemness...

Area of Science:

• Molecular Biology
• Oncology
• Gene Regulation

Background:

• Circular RNAs (circRNAs) are increasingly recognized for their roles in various biological processes, including cancer.
• The specific functions and regulatory mechanisms of many circRNAs, such as hsa_circ_0005963, in non-small cell lung cancer (NSCLC) remain largely unexplored.
• Understanding these mechanisms is crucial for developing novel therapeutic strategies against NSCLC.

Purpose of the Study:

• To investigate the role and regulatory mechanisms of hsa_circ_0005963 in the development and progression of non-small cell lung cancer (NSCLC).
• To determine the clinical significance of hsa_circ_0005963 expression in NSCLC patients.

Main Methods:

• Quantitative real-time PCR (RT-qPCR) and fluorescence in situ hybridization (FISH) were utilized to measure hsa_circ_0005963 expression levels in NSCLC tissues and cells.
• Functional assays, including Transwell migration and EdU incorporation, were performed to assess the impact of hsa_circ_0005963 on NSCLC cell proliferation and migration.
• A dual-luciferase reporter assay identified downstream targets, and a mouse tumor xenograft model was used to evaluate hsa_circ_0005963's role in vivo.

Main Results:

• hsa_circ_0005963 expression was significantly upregulated in NSCLC tissues and cells, correlating with poor overall survival.
• Silencing hsa_circ_0005963 inhibited NSCLC cell proliferation, migration, and invasion, including in A549 cell lines.
• The study identified SOX9 and miR-506-3p as direct downstream targets of hsa_circ_0005963, with SOX9 overexpression or miR-506-3p downregulation reversing the inhibitory effects of hsa_circ_0005963 silencing.

Conclusions:

• hsa_circ_0005963 acts as a tumor promoter in NSCLC by acting as a molecular sponge for miR-506-3p, thereby upregulating SOX9 expression.
• These findings elucidate a novel regulatory pathway involving hsa_circ_0005963, miR-506-3p, and SOX9 in NSCLC pathogenesis.
• hsa_circ_0005963 represents a potential diagnostic biomarker and therapeutic target for NSCLC.