circFANCA accelerates the malignant process of OSCC by modulating miR-34a/PA28γ signaling

• Published in: Biochemical and biophysical research communications Vol. 665; pp. 45 - 54
• Main Authors: Ren, Yuan, Pan, Keran, Wang, Ying, Zhang, Shiyu, Wang, Yimei, Zhou, Xikun, Dan, HongXia, Chen, Qianming, Ji, Ning, Li, Jing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.07.2023
• Subjects: Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; circFANCA; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; miR-34a; Oral squamous cell carcinoma; PA28γ; Prognostic biomarkers; Signal Transduction; Prognostic biomarkers; PA28γ; circFANCA; Oral squamous cell carcinoma; miR-34a
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2023.04.084

To investigate the upstream regulatory molecules of proteasomal activator 28γ (PA28γ), and explore its specific regulatory mechanism and potential clinical significance in OSCC. qPCR was used to examine miR-34a, circFANCA and PSME3 expression. Western blotting was adopted to detect PA28γ expression. Transwell experiments were conducted to evaluate OSCC cell migration and invasion ability. FISH was used to evaluate the subcellular localization of circFANCA and miR-34a, and RNA pull-down verified the interaction between them. The expression of circFANCA and miR-34a in clinical cohorts was assessed by ISH, and the results were subjected to survival analysis using Kaplan-Meier analysis. Here, we proved that miR-34a expression is lower in highly aggressive OSCC tissues and cell lines. Notably, miR-34a can downregulate PA28γ expression and inhibit OSCC invasion and migration. Next, we confirmed that circFANCA promoted OSCC cell metastatic ability by sponging miR-34a. Importantly, interfering with miR-34a rescued the malignant progression of OSCC induced by silencing circFANCA. Finally, clinical data showed lower miR-34a expression and higher circFANCA expression were associated with poor prognosis in OSCC patients. The circFANCA/miR-34a/PA28γ axis facilitates the metastasis of OSCC, and circFANCA and miR-34a have potential to serve as prognostic markers for OSCC patients. [Display omitted] •CircFANCA directly targeted miR-34a.•CircFANCA mediated PA28γ expression through miR-34a.•CircFANCA silencing inhibited OSCC progression by the miR-34a/PA28γ axis.