Research Paper Volume 12, Issue 20 pp 20396—20412
The oncogenic role of LncRNA FAM83C-AS1 in colorectal cancer development by epigenetically inhibits SEMA3F via stabilizing EZH2
- 1 Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China
- 2 Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin 150081, China
- 3 Department of Pharmacology and Toxicology, Wright State University, Fairborn, OH 45435, USA
Received: April 28, 2020 Accepted: July 14, 2020 Published: October 27, 2020
https://doi.org/10.18632/aging.103835How to Cite
Copyright: © 2020 Xue 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.
Abstract
Inactivation of Semaphorin 3F (SEMA3F) is involved in colorectal cancer development. However, the mechanism by which SEMA3F is regulated remains elusive. Deregulation of lncRNAs have been implicated in multiple human malignancies, including colorectal cancer (CRC). To date, it is still unclear whether and how lncRNA regulates SEMA3F expression and mediates CRC progression. Here we identify the oncogenic role of lncRNA FAM83C antisense RNA 1 (FAM83C-AS1) in CRC. FAM83C-AS1 is upregulated in tumor tissues and cells of CRC, which is negatively correlated with SEMA3F expression. Reciprocally, knockdown of FAM83C-AS1 exhibits inhibitory effects on the malignant transformation of CRC. Moreover, our data uncover that FAM83C-AS1 enhances methylation of SEMA3F promoter H3K27me3 via upregulating methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2). Specifically, FAM83C-AS1 stabilizes EZH2 protein through recruiting the zinc finger RANBP2-type containing 1 (ZRANB1). Both in vitro and in vivo rescue assays exhibit that SEMA3F is dispensable for the tumor-promoting effects of FAM83C-AS1 on CRC progression. Our data thus demonstrate that the epigenetic role of FAM83C-AS1 in suppression of SEMA3F expression through stabilization of EZH2 to drive CRC progression, which may be conducive to discovering novel therapeutic targets for the treatment of CRC.