Circular RNA circ_0065378 upregulates tumor suppressor candidate 1 by competitively binding with miR-4701-5p to alleviate colorectal cancer progression.

BACKGROUND AND AIM

Colorectal cancer (CRC), the third most lethal human cancer worldwide, seriously threatens human health and life. Numerous circular RNAs (circRNAs) including circ_PLXNB1 (hsa_circ_0065378) have been confirmed to be dysregulated in CRC by RNA-seq analysis. We aimed to explore the functional role of circ_PLXNB1 in CRC malignant behaviors and clarify its potential molecular mechanism.

METHODS

Gene expression levels of circ_PLXNB1 and miR-4701-5p were determined by quantitative real-time polymerase chain reaction analysis. MTT and Transwell assays were conducted to measure cell proliferation, invasion, and migration. Protein expression of tumor suppressor candidate 1 (TUSC1), E-cadherin and N-cadherin was determined by western blot analysis. Mouse xenograft models were used to investigate the role of circ_PLXNB1 in tumor growth.

RESULTS

The results showed that gene expression of circ_PLXNB1 in CRC tissues was significantly downregulated. Overexpression of circ_PLXNB1 inhibited the malignant behaviors of CRC cells, as manifested by the decrease in cell proliferation, cell invasion, migration, and EMT. Mechanistically, circ_PLXNB1 exerted its functional effects by binding with miR-4701-5p. Moreover, TUSC1 siRNA partially abolished the suppressive effect of the miR-4701-5p inhibitor or circ_PLXNB1 on CRC cell malignant behaviors.

CONCLUSIONS

Circ_PLXNB1 attenuated CRC progression by binding with miR-4701-5p to overexpress TUSC1, indicating that the circ_PLXNB1/miR-4701-5p/TUSC1 axis might be a potential novel molecular target in CRC diagnosis and therapy.