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

环状 RNA circ_0065378 通过与 miR-4701-5p 竞争性结合来上调肿瘤抑制候选基因 1,从而缓解结直肠癌进展

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作者:Dongsheng Yan, Weidong Liu, Yeliu Liu, Xinguo Zhu

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.

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.

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.

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