Research Paper Volume 11, Issue 19 pp 8068—8084
A circular RNA from APC inhibits the proliferation of diffuse large B-cell lymphoma by inactivating Wnt/β-catenin signaling via interacting with TET1 and miR-888
- 1 Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
- 2 Endoscopic Center, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
received: May 5, 2019 ; accepted: July 21, 2019 ; published: October 13, 2019 ;https://doi.org/10.18632/aging.102122
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Copyright © 2019 Hu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Circular RNA (circRNA), a type of non-coding RNA, can promote or suppress tumorigenesis. To investigate the involvement of circRNA in diffuse large B-cell lymphoma (DLBCL), we performed a circRNA microarray analysis on paired DLBCL and normal tissues. We identified a novel and highly stable circRNA originating from the back-splicing of APC exon 7 to exon 14, circ-APC (hsa_circ_0127621), which was downregulated in DLBCL tissues, cell lines and plasma. In gain-of-function experiments, ectopic expression of circ-APC inhibited DLBCL cell proliferation in vitro and tumor growth in vivo. Cytoplasmic circ-APC functioned as a sponge for miR-888, thus post-transcriptionally upregulating APC by alleviating the repressive effects of miR-888 on this gene. Further, nuclear circ-APC bound to the APC promoter and recruited the DNA demethylase TET1, thereby transcriptionally upregulating APC. Upon its upregulation, APC dampened the canonical Wnt/β-catenin signaling pathway by reducing the accumulation of β-catenin in the nucleus, thereby retarding DLBCL growth. Clinically, circ-APC was found to be an effective diagnostic and prognostic biomarker for patients with DLBCL. Our study suggests that circ-APC is a novel proliferation inhibitor, and that restoring circ-APC expression may be a promising therapeutic approach for DLBCL patients.