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

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-520 h (miR-520 h) 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-520 h or miR-520 h 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-520 h, and HK1 was the target of miR-520 h. Meanwhile, miR-520 h inhibitor reversed the inhibitory effect of circ_0053277 silencing on CRC cell progression, and HK1 overexpression also overturned the suppressive effect of miR-520 h on CRC cell growth, angiogenesis and metastasis. Moreover, circ_0053277 knockdown inhibited the glycolysis of CRC cells by regulating miR-520 h/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-520 h/HK1 pathway, confirming that circ_0053277 might be a potential clinical target for CRC treatment.

Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.