circIFT80 Functions as a ceRNA of miR-1236-3p to Promote Colorectal Cancer Progression
Molecular Therapy - Nucleic Acids , Volume 18, pp 375-387; doi:10.1016/j.omtn.2019.08.024
Abstract: Circular RNAs (circRNAs), a recently identified new member of non-coding RNAs, are demonstrated to participate in diverse biological processes; however, the molecular mechanisms that link circRNAs with colorectal cancer (CRC) are not well understood. In the present study, we attempted to explore the roles of the exosomal circRNAs on CRC progression. We first compared the expression patterns of exosomal circRNAs between the plasma of CRC patients and healthy controls. We identified 448 significantly dysregulated exosomal circRNAs in CRC plasma. We focused on hsa_circ_0067835, which is located on chromosome 3 and derived from IFT80; thus, we named it circIFT80. Then, the expression of circIFT80 was detected in 58 CRC tissues and cell lines by qRT-PCR. Functional assays were performed to evaluate the effects of circIFT80 on tumor growth in vitro and in vivo. The relationship between circIFT80 and miR-1236-3p was confirmed by luciferase reporter assay. We found that circIFT80 was significantly upregulated in CRC serum exosomes, CRC tissues, and CRC cell lines compared with normal control. Silencing circIFT80 suppressed CRC cell growth both in vitro and in vivo. We further demonstrated that circIFT80/miR-1236-3p/HOXB7 axis plays an important role in regulating CRC progression. Dual-luciferase reporter system validated the direct interaction of circIFT80, miR-1236-3p, and HOXB7. Western blot verified that inhibition of circIFT80 decreased HOXB7 expression, while a miR-1236-3p inhibitor attenuated the effect of inhibition of circIFT80. In conclusion, these data suggest that circIFT80 is a central component linking circRNAs to the progression of CRC via a miR-1236-3p/HOXB7 axis.
Keywords: CRC; exosome; circRNAs; circIFT80; ceRNA; HOXB7
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