CircBFAR correlates with poor prognosis and promotes laryngeal squamous cell cancer progression through miR‐31‐5p/COL5A1 axis

Abstract

Introduction: Laryngeal squamous cell cancer (LSCC) is a highly malignant tumor originating from the respiratory system. Circular RNAs have been reported to be associated with the treatment and prognosis of a variety of cancers, including LSCC. Methods:The expression of circBFAR, miR-31-5p, and collagen type V alpha 1 chain (COL5A1) in LSCC tissues and cells was detected by quantitative real-time polymerase chain reaction. Cell counting kit 8 and 5-Ethynyl-2 0 -deoxyuridine assays were used to detect cell proliferation. Wound healing assay and transwell assay were used to test cell migration and invasion, respectively. The protein expression in LSCC cells was detected with western blot. The relationships between miR-31-5p and circBFAR or COL5A1 were identified by dual-luciferase reporter assay, RNA-pull down assay, and immunoprecipitation assay. The effect of circBFAR on tumor growth in vivo was detected by tumor xenograft mice experiment. The protein expression of COL5A1 and KI-67 in LSCC tissues was measured by immunohistochemistry assay. Results: CircBFAR was increased in LSCC tissues and cells, and was related to advanced clinical stage and overall survival of LSCC patients. The cell viability and proliferation were inhibited by circBFAR knockdown and silencing of circBFAR blocked migration and invasion of LSCC cells. CircBFAR knockdown suppressed cell tube formation, and the protein expression of KI-67, matrix metallopeptidase 2 (MMP2), and vascular endothelial growth factor A (VEGFA) in LSCC cells. MiR-31-5p was the target of circBFAR, and the inhibitory effects of circBFAR deficiency on viability, proliferation, migration, invasion, tube formation and the protein expression of KI-67, MMP2, and VEGFA in LSCC cells were rescued by miR-31-5p downregulation. COL5A1 was negatively regulated by miR-31-5p, and was boosted in LSCC tissues and cells. COL5A1 overexpression reversed the inhibitory effects of miR-31-5p on LSCC cells. CircBFAR insufficiency hindered tumor growth in vivo. Conclusion: CircBFAR, miR-31-5p, and COL5A1 in LSCC progression might provide novel therapeutic targets for LSCC clinical intervention. Hengcui Gong and Wei Wu contribute to this work equally as co-first authors.

High hsa_circ_0081621 expression indicates a poor prognosis of laryngeal squamous cell carcinoma: A bioinformatics analysis and retrospective clinical study

“…For example, as an oncogenic RNA, circ coronin 1C can serve as a novel target for LSCC treatment and may act as a diagnostic and prognostic marker for LSCC detection ( 14 ). Circ bifunctional apoptosis regulator is associated with poor prognosis and accelerated LSCC progression ( 27 ). circ_0067934 is an oncogene promoting LSCC and may be a viable prognostic biomarker and target for diagnosis and treatment ( 28 ).…”

Exploring the evolving roles and clinical significance of circRNAs in head and neck squamous cell carcinoma

“…Given that VEGF is pivotal in promoting cancer cell growth through angiogenesis, circRNAs exert influence by directly or indirectly modulating VEGF expression levels 95 , 96 . Gong et al discovered that circBFAR promotes ki-67, MMP2, and VEGFA protein expression by binding to miR-31-5p, facilitating the generation of new blood vessels in LSCC 97 . In LSCC, silencing circSHKBP1 leads to a significant reduction in MMP2 and VEGFA expression, resulting in the inhibition of LSCC cell invasion and angiogenesis 98 .…”