CircPRRC2C Promotes the Oncogenic Phenotypes of Laryngeal Squamous Cell Carcinoma Cells via MiR-136-5p/HOXD11 Axis

The involvement of circular RNAs (circRNAs) in laryngeal squamous cell carcinoma (LSCC) carcinogenesis has gradually been proposed. Herein, we aimed to explore the function and mechanism of circPRRC2C in LSCC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used for detecting the content of genes and proteins. In vitro experiments were conducted using 5-ethynyl-2 & PRIME;-deoxyuridine, colony formation, flow cytometry, and transwell assays. The binding between miR-136-5p and circPRRC2C or Homeobox D11 (HOXD11) was confirmed by using the dual-luciferase reporter assay. The murine xenograft model was established for in vivo analysis. The commercial kit was used for exosome separation. CircPRRC2C is a stable circRNA, and was highly expressed in LSCC tissues and cell lines. Functionally, circPRRC2C deficiency impaired LSCC cell proliferation, migration and invasion but induced cell apoptosis in vitro and impeded tumor growth in vivo, however, circPRRC2C overexpression showed the exact opposite effects. Mechanistically, circPRRC2C directly targeted miR-136-5p, which showed inhibitory effects on the growth and mobility of LSCC cells. Meanwhile, miR-136-5p directly targeted HOXD11, and circPRRC2C/miR-136-5p/HOXD11 formed a feedback loop in LSCC cells. Further rescue assays exhibited that circPRRC2C exerted its effects by miR-136-5p/HOXD11 axis. In addition, circPRRC2C was stably packaged into exosomes and showed potential diagnostic value for LSCC. CircPRRC2C acted as an oncogene to promote LSCC cell oncogenic phenotypes via miR-136-5p/HOXD11 axis, besides, circPRRC2C was stably packaged into exosomes, indicating the potential application of circPRRC2C-targeting agents in the treatment in LSCC.

Automated summary

The study found that circPRRC2C plays an important role in the carcinogenesis of laryngeal squamous cell carcinoma (LSCC). CircPRRC2C is highly expressed in LSCC tissues and cells, and its deficiency impairs LSCC cell proliferation, migration, and invasion while inducing cell apoptosis and inhibiting tumor growth. CircPRRC2C acts as an oncogene by regulating the miR-136-5p/HOXD11 axis to promote the oncogenic phenotypes of LSCC cells. Additionally, circPRRC2C can be stably packaged into exosomes and may have potential diagnostic value for LSCC.