Cutaneous squamous cell carcinoma (CSCC) is the most common metastatic skin cancer. Circular RNAs (circRNAs) are differentially expressed in CSCC and can sequester and sponge microRNAs. GSE74758 shows that hsa_circ_0001402 (circ_0001402) is the most overexpressed circRNA in CSCC. Expression of circ_0001402, microRNA(miR)-625-5p and karyopherin subunit alpha 4 (KPNA4) was detected by quantitative real-time polymerase chain reaction and/or Western blot. Colon formation, flow cytometry, Transwell assays and xenograft tumour model confirmed the development of CSCC cells. The competing endogenous RNA (ceRNA) interaction was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Circ_0001402 was significantly upregulated in CSCC tissues and cells, and higher expression of circ_0001402 was found in DDP-resistant samples. Functionally, circ_0001402 knockdown induced apoptosis and inhibited half maximal inhibitory concentration of DDP, colony formation, migration and invasion of DDP-resistant CSCC cells, accompanied with the depressed multi-drug resistance-1 (MDR1) and MDR-related protein-1, while miR-625-5p inhibitor could counteract these effects. Mechanically, circ_0001402 mediated the expression regulation of KPNA4 via functioning as a ceRNA for miR-625-5p. KPNA4 re-expression could abate the functions of miR-625-5p. Furthermore, circ_0001402 knockdown could hinder tumour growth of DDP-resistant CSCC. Circ_0001402 knockdown can suppress the development and chemoresistance of DDP-resistant CSCC cells at least partly through targeting miR-625-5p/KPNA4 axis.
Keywords: Circ_0001402; DDP-resistant CSCC; KPNA4; miR-625-5p.
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