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.

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.