circ5615 functions as a ceRNA to promote colorectal cancer progression by upregulating TNKS.

Abstract

Circular RNAs (circRNAs), non-coding RNAs generated by precursor mRNA back-splicing of exons, have been reported to fulfill multiple roles in cancer. However, the role of quite a lot circRNAs in colorectal cancer (CRC) remains mostly unknown. Herein, we explored the expression profiles of circRNAs in 5 paired samples of CRC patients by microarray and noted a circRNA, hsa_circ_0005615 (circ5615), was significantly upregulated in CRC tissues. Circ5615 was derived from exon 2 of NFATC3 and its upregulation was tightly correlated with higher T stage and poor prognosis in CRC patients. Studies in vitro and in vivo demonstrated that knockdown of circ5615 in cancer cells inhibited proliferation and cell cycle acceleration, while overexpression promoted malignant phenotypes. Mechanistically, RNA immunoprecipitation, biotin-coupled probe pull-down and luciferase reporter assays revealed circ5615 effectively bound to miR-149-5p and might play a role like miR-149-5p sponge. Additionally, tankyrase (TNKS), regulator of β-catenin stabilization, was identified as circ5615 downstream and the potential miR-149-5p targets by RNA-seq and bioinformatics analysis. We further verified the upregulation of β-catenin and cyclin D1 induced by circ5615. Our results indicated that circ5615 exerted oncogenic function as competing endogenous RNA (ceRNA) of miR-149-5p to release TNKS and activated Wnt/β-catenin pathway.

• Authors: Zhifei Ma, Chencheng Han, Wenjia Xia, Siwei Wang, Xiang Li, Panqi Fang, Rong Yin, Lin Xu, Liu Yang
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 5 Pg. 356 (05 11 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 32393760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCND1 protein, human
• CTNNB1 protein, human
• MIRN149 microRNA, human
• MicroRNAs
• RNA, Circular
• beta Catenin
• Cyclin D1
• Tankyrases
• TNKS protein, human

Topics

• Animals
• Cell Cycle
• Cell Proliferation
• Colorectal Neoplasms (enzymology, genetics, pathology)
• Cyclin D1 (genetics, metabolism)
• Disease Progression
• Gene Expression Regulation, Neoplastic
• HCT116 Cells
• HT29 Cells
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• RNA, Circular (genetics, metabolism)
• Tankyrases (genetics, metabolism)
• Tumor Burden
• Up-Regulation
• Wnt Signaling Pathway
• beta Catenin (genetics, metabolism)