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

Dongsheng Yan, Weidong Liu, Yeliu Liu, Xinguo Zhu

Journal of gastroenterology and hepatology 2022 Jun

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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. 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. 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. 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. © 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Citation

Dongsheng Yan, Weidong Liu, Yeliu Liu, Xinguo Zhu. Circular RNA circ_0065378 upregulates tumor suppressor candidate 1 by competitively binding with miR-4701-5p to alleviate colorectal cancer progression. Journal of gastroenterology and hepatology. 2022 Jun;37(6):1107-1118