Circular RNA (circ)_0053277 Contributes to Colorectal Cancer Cell Growth, Angiogenesis, Metastasis and Glycolysis.

Abstract

Circular RNAs (circRNAs) have been found to be abnormally expressed in many cancers, including colorectal cancer (CRC). Circ_0053277 has been found to mediate CRC malignant processes and may be a key regulator for CRC progression. Therefore, its role and potential molecular mechanism in CRC process deserve further investigation. Quantitative real-time PCR was used to detect the expression levels of circ_0053277, microRNA-520h (miR-520h) and hexokinase 1 (HK1). Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, wound healing assay, transwell assay, and tube formation assay were used to detect CRC cell proliferation, apoptosis, migration, invasion, and angiogenesis. The protein levels of apoptosis-related markers and HK1 were detected by western blot. The relationship between circ_0053277 and miR-520h or miR-520h and HK1 in CRC cells was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Cell glycolysis was assessed by detecting glucose uptake and lactate production. The effect of silenced circ_0053277 on CRC tumor growth was evaluated by xenograft model in vivo. Our study found that circ_0053277 expression was elevated in CRC tissues and cells. Moreover, circ_0053277 knockdown suppressed CRC cell proliferation, angiogenesis, migration and invasion, while promoting apoptosis. In terms of mechanism, circ_0053277 sponged miR-520h, and HK1 was the target of miR-520h. Meanwhile, miR-520h inhibitor reversed the inhibitory effect of circ_0053277 silencing on CRC cell progression, and HK1 overexpression also overturned the suppressive effect of miR-520h on CRC cell growth, angiogenesis and metastasis. Moreover, circ_0053277 knockdown inhibited the glycolysis of CRC cells by regulating miR-520h/HK1 pathway. In addition, knockdown of circ_0053277 reduced CRC tumor growth in vivo. Circ_0053277 promoted CRC cell growth, angiogenesis, metastasis and glycolysis by miR-520h/HK1 pathway, confirming that circ_0053277 might be a potential clinical target for CRC treatment.