Circ_0067717 promotes colorectal cancer cell growth, invasion and glutamine metabolism by serving as a miR-497-5p sponge to upregulate SLC7A5

• Mo Song ^[1] ; Jipan Liu ^[1]
  1. [1] Hengshui People’s Hospital, Hengshui, China
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 38, Nº. 1, 2023, págs. 53-64
• Idioma: inglés
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• Resumen

  • Background. Circular RNAs (circRNAs) have been shown to exert vital functions in colorectal cancer (CRC) development. However, the role of circ_0067717 in CRC progression remains to be elucidated.

    Methods. The expression of circ_0067717, microRNA (miR)-497-5p and solute carrier family 7 member 5 (SLC7A5) was analyzed by quantitative realtime PCR. Cell proliferation, apoptosis and invasion were determined by cell counting kit 8 assay, EdU assay, flow cytometry and transwell assay. Protein expression was examined using western blot analysis. Glutamine metabolism was assessed by measuring glutamine consumption, α-ketoglutarate production and glutamate production. The interaction between miR-497-5p and circ_0067717 or SLC7A5 was identified by dualluciferase reporter assay. Xenograft tumor models were constructed to confirm the role of circ_0067717 in CRC tumorigenesis in vivo.

    Results. Our data revealed that circ_0067717 was upregulated in CRC tissues and cells, and its knockdown restrained CRC cell proliferation, invasion, glutamine metabolism, and promoted apoptosis. MiR-497-5p was lowly expressed in CRC and it could be sponged by circ_0067717. MiR-497-5p inhibitor eliminated the regulation of circ_0067717 knockdown on CRC cell function. SLC7A5 was targeted by miR-497-5p and was positively regulated by circ_0067717. MiR-497-5p overexpression suppressed CRC cell growth, invasion and glutamine metabolism, and SLC7A5 was able to revoke this effect. Animal experiments showed that interference of circ_0067717 reduced CRC tumor growth.

    Conclusion. Our research pointed out that circ_0067717 facilitated CRC development depending on the regulation of the miR-497-5p/SLC7A5 axis, providing a novel insight into CRC treatment.