Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR-149-5p/IL-6/STAT3 pathway

Abstract

Circular RNAs (circRNAs) are novel noncoding RNAs (ncRNAs) with covalently closed-loop structures that play an essential regulatory role in diverse malignancies, including esophageal squamous cell cancer (ESCC). Circ_0000654 expression in ESCC and its mechanism of action remains unclear. Real-time PCR (RT-PCR) was employed to detect circ_0000654 and miR-149-5p expression in ESCC tissues. Circ_0000654 and miR-149-5p expression in ESCC cells was selectively regulated. Furthermore, interleukin 6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) expression in cells was detected by RT-PCR and western blot analysis, while CCK8, BrdU, flow cytometry, and transwell assays were used to monitor cell proliferation, apoptosis, migration and invasion, respectively. The dual-luciferase reporter assay and RIP assay were used to verify the targeting relationship between circ_0000654 and miR-149-5p, miR-149-5p and IL-6. The function of circ_0000654 on ESCC cell proliferation and metastasis in vivo was examined using a subcutaneous xenograft model and a tail intravenous injection model in nude mice. Circ_0000654 was significantly upregulated in ESCC tissues and cell lines, and its high expression was remarkably associated with an increased T stage and local lymph node metastasis in ESCC patients. Circ_0000654 overexpression and knockdown experiments revealed that circ_0000654 regulated ESCC cell proliferation, migration, invasion, and apoptosis in vitro. Circ_0000654 was identified as a sponge of miR-149-5p and facilitated ESCC progression by indirectly activating the IL-6/STAT3 signaling pathway. Additionally, knocking down circ_0000654 strikingly repressed ESCC growth and metastasis in vivo. In summary, circ_0000654 functions as an oncogenic circRNA in ESCC and accelerates ESCC progression via adsorbing miR-149-5p and activating the IL-6/STAT3 signaling pathway.