Abstract

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a “sponge” of miR-31, indirectly regulating Wnt/β-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/β-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

Highlights

  • Colorectal cancer has the third highest incidence rate and fourth highest mortality rate among all cancer cases [1]

  • The regulating mechanism of circular RNA (circRNA) in cancer was investigated in several studies: in esophageal squamous cell carcinoma (ESCC), cir-ITCH acted as sponge of miRNAs to both increase the level of ITCH and inhibit the Wnt/b-catenin pathway, inhibiting ESCC [14]; in breast cancer cells (MDAMB-231), circ-Foxo3 bonded with 8 miRNAs to promote the translation of Foxo3 mRNA, inhibiting cell proliferation [22]

  • It was previously found that RNA-seq showed a global reduction of circRNA abundance in both colorectal cancer cell lines and tissues [23]

Read more

Summary

Introduction

Colorectal cancer has the third highest incidence rate and fourth highest mortality rate among all cancer cases [1]. Common treatments of colorectal cancer such as surgical resection, radiotherapy, chemotherapy or their combination extend life expectancy for up to 5 years, mortality and recurrence rates are high. It is, important to develop new molecular biomarkers and targets for more effective treatments. The regulating mechanism of circRNA in cancer was investigated in several studies: in esophageal squamous cell carcinoma (ESCC), cir-ITCH acted as sponge of miRNAs to both increase the level of ITCH and inhibit the Wnt/b-catenin pathway, inhibiting ESCC [14]; in breast cancer cells (MDAMB-231), circ-Foxo (hsa_circRNA_104170) bonded with 8 miRNAs (miR-22, miR-136, miR-138, miR-149, miR-433, miR-762, miR-3614-5, and miR-3622b-5p) to promote the translation of Foxo mRNA, inhibiting cell proliferation [22]. Bachmayr-Heyda and colleagues observed a globally lower expression of circRNAs in colorectal cancer cells compared to their healthy counterparts; a negative correlation between the circRNA abundance and the proliferation of colorectal cancer cells was determined by the team [23]

Objectives
Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call