Circ_0101802 Facilitates Colorectal Cancer Progression Depending on the Regulation of miR-665/DVL3 Signaling

Biochem Genet. 2022 Dec;60(6):2250-2267. doi: 10.1007/s10528-022-10207-6. Epub 2022 Mar 21.

Abstract

Colorectal cancer (CRC) is a common malignancy in both men and women, and the prognosis of CRC patients is still unsatisfactory. We aimed to identify novel effective diagnostic and prognostic targets for CRC. The study design is listed as below: we first confirmed the linear correlation between the expression of disheveled 3 (DVL3) and circular RNA_0101802 (circ_0101802) in CRC tissues, and their functional correlation in CRC cells was verified by rescue assays. Subsequently, bioinformatics databases were used to search the common interacted microRNAs (miRNAs) of DVL3 and circ_0101802, and compensation experiments were conducted to verify the functional correlation between miR-665 and DVL3 in CRC cells. Finally, xenograft tumor model was established to confirm the role of circ_0101802/miR-665/DVL3 axis in tumor growth in vivo. The expression of DVL3 and circ_0101802 was elevated in CRC tissues and cell lines, and high levels of DVL3 and circ_0101802 were closely associated with short survival time of CRC patients. Circ_0101802 silencing restrained the proliferation, migration, and tube formation abilities and induced the apoptosis of CRC cells. Circ_0101802 silencing-induced anti-tumor effects in CRC cells were partly reversed by DVL3 overexpression. miR-665 was an intermediary molecule between circ_0101802 and DVL3, and circ_0101802 could positively regulate DVL3 protein expression by sponging miR-665 in CRC cells. DVL3 overexpression partly overturned miR-665 overexpression-mediated anti-tumor effects in CRC cells. Circ_0101802 knockdown significantly suppressed xenograft tumor growth in vivo. In conclusion, circ_0101802 contributed to CRC progression by targeting miR-665/DVL3 signaling.

Keywords: Colorectal cancer; DVL3; circ_0101802; miR-665.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms* / metabolism
  • Dishevelled Proteins* / genetics
  • Dishevelled Proteins* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular* / genetics

Substances

  • Dishevelled Proteins
  • DVL3 protein, human
  • MicroRNAs
  • MIRN665 microRNA, human
  • RNA, Circular