Yonsei Med J.  2019 Dec;60(12):1117-1128. 10.3349/ymj.2019.60.12.1117.

Circular RNAs Regulate Cancer Onset and Progression via Wnt/β-Catenin Signaling Pathway

• Li YF
• Zhang J
• Yu L

• KMID: 2463790
• DOI: http://doi.org/10.3349/ymj.2019.60.12.1117

Abstract

Cancer remains to be a major challenge for public health providers, and is the second leading cause of death worldwide. Therefore, it is imperative to explore the mechanisms underlying cancer initiation and development, and design novel diagnostics and therapeutics. Circular RNAs (circRNAs), which exhibit a covalently closed loop structure, are involved in a variety of diseases, including cancer. The aberrant expression of circRNAs contributes to the initiation and development of various cancers by disrupting the interplay of specific signaling pathways, including the Wnt/β-catenin pathway, which controls a plethora of cellular processes that drive cancer development. The interactions between circRNAs (specifically expressed in different cancer tissues) and Wnt/β-catenin signaling pathway presents potential diagnostic biomarkers and novel therapeutic targets. In this review, we have summarized research discoveries on the functions of Wnt/β-catenin pathway-related circRNAs in the modulation of oncogenesis and progression of different types of cancer. We anticipate that our findings will contribute to the improvement or development of circRNAs-based strategies for cancer treatment.

Keyword

Circular RNA; cancer; Wnt/β-catenin signaling pathway

MeSH Terms

Biomarkers
Carcinogenesis
Cause of Death
Public Health
RNA*
Biomarkers
RNA

Figure

• 

  Fig. 1 Diverse regulatory mechanisms of circRNAs and Wnt/β-catenin signaling pathway. Circ_0006427 inactivates Wnt/β-catenin pathway by upregulating Dkk1 in a miR-6783-3p-dependent manner; Circ_ITCH may increase the expression of protein ITCH by binding to miR-7, miR-20, and miR-124. Subsequently, overexpressed ITCH downregulates Dvl, which reduces β-catenin degradation and activates this pathway. Three circRNAs (circRNA_NEK6, circ_CBFB and circ_0067934) upregulate frizzled (FZD) expression by sponging corresponding miRNAs (miR-370-3p, miR-607 and miR-1324), and thereby activating the pathway. Hsa_circ_009361 and hsa_circ_0002052 also increase APC2 expression by sponging miR-582 and miR-1205, which inactivates Wnt/β-catenin cascade. Circβ-catenin encodes a β-catenin isoform, termed “β-catenin-370-aa”, to enhance the stability of β-catenin by reducing GSK3β-induced β-catenin phosphorylation and degradation, and thereby activating Wnt/β-catenin signaling pathway. CircRNA cZNF292 directly upregulates the expression of β-catenin, thereby activating Wnt/β-catenin signaling pathway, but it also suppresses some inhibitors of this pathway, such as APC and Axin. CircRNA_102171 reduces the level of CTNNBIP1 in the nucleus, and enhances the association between β-catenin and TCF/LEF to upregulate Wnt/β-catenin signaling pathway.

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