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Circular RNAs (circRNAs) are implicated in diverse human cancers. However, the effects of circRNAs on cutaneous squamous cell carcinoma (CSCC) are barely known. We focused on the function of circ_0001821 in CSCC. Quantitative reverse transcription PCR was performed for the expression of circ_0001821, miR-148a-3p, and epidermal growth factor receptor (EGFR). Cell counting kit-8 assay and colony formation assay were conducted to evaluate cell viability and colony formation ability. Flow cytometry analysis was adopted to analyze cell cycle and apoptosis. A transwell assay was employed to detect cell motility. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pulldown assay were utilized to verify the interaction between miR-148a-3p and circ_0001821 or EGFR. A Western blot assay was conducted for protein levels. Murine xenograft model assay was used to explore the function of circ_0001821  in vivo . circ_0001821 level was increased in CSCC tissues and cells. circ_0001821 knockdown restrained cell viability, colony formation, cell cycle processes, and metastasis, and facilitated cell apoptosis  in vitro , and restrained tumor growth  in vivo . For mechanism analysis, circ_0001821 directly targeted miR-148a-3p to elevate EGFR expression. Downregulation of miR-148a-3p weakened the impacts of circ_0001821 deficiency on CSCC malignant phenotypes. Moreover, miR-148a-3p overexpression inhibited the malignant phenotypes of CSCC cells, with EGFR elevation abrogating the effects. In addition, circ_0001821 knockdown blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. circ_0001821 functioned as a tumor promoter in CSCC via regulating the miR-148a-3p/EGFR axis and PI3K/Akt pathway.

molecular and cellular biology

circ_0001821 Contributes to the Development of Cutaneous Squamous Cell Carcinoma by Regulating MicroRNA-148a-3p/EGFR Axis and Activating Phosphatidylinositol 3-Kinase/Akt Pathway