Novel circular RNA hsa_circ_0077837 suppresses colorectal cancer cell proliferation by regulating the microRNA 21/phosphatase and tensin homolog axis

Abstract

Background: Circular RNA (circRNA) is a novel noncoding RNA (ncRNA) that assumes critical roles in tumor occurrence and progression. circRNA functions in many tumors as a kind of microRNA (mRNA) “sponge.” The present study sought to investigate the part played by circRNA in colorectal cancer (CRC) progression and to elucidate the relevant action mechanism(s). Methods: We detected lower hsa_circ_0077837 (circEPB41L2) expression in CRC by data analysis based on previous studies. We demonstrated the antitumor part of circEPB41L2 in CRC cells via a group of biological experiments. We subsequently took advantage of pull-down and dual-luciferase reporter assays to recognize circEPB41L2 downstream microRNA 21 (miR-21). Western blotting was conducted to confirm that the circEPB41L2–miR-21–phosphatase and tensin homolog (Pten)/AKT axis is responsible for CRC tumor growth suppression. The antitumor part of circEPB41L2 in vivo was eventually demonstrated by HCT116 xenograft model. Results: We found that circEPB41L2 overexpression inhibited the proliferation of CRC cells. Further, the miR-21 phenocopy suppressed circNRIP1 overexpression, while its overexpression also inhibited the cancer suppressive function of circEPB41L2. circEPB41L2 was confirmed to be able to inhibit tumor growth by enhancing Pten expression. Finally, the antitumor part of circEPB41L2 was confirmed. Conclusions: We demonstrated that circEPB41L2 sponges miR-21 to increase the Pten expression level and consequently serve as a cancer suppressor in CRC.