Circular RNA TMEM87A promotes cell proliferation and metastasis of gastric cancer by elevating ULK1 via sponging miR-142
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ORIGINAL ARTICLE—ALIMENTARY TRACT
Circular RNA TMEM87A promotes cell proliferation and metastasis of gastric cancer by elevating ULK1 via sponging miR-142-5p Haixiao Wang1,3 • Guangli Sun1 • Penghui Xu1 • Jialun Lv1 • Xing Zhang1 Lu Zhang1 • Sen Wang1 • Jiacheng Cao1 • Yiwen Xia1 • Zhe Xuan1 • Bowen Li1 • Xiaoxu Huang1 • Tianlu Jiang1 • Lang Fang1 • Zekuan Xu1,2
•
Received: 8 July 2020 / Accepted: 20 October 2020 Ó Japanese Society of Gastroenterology 2020
Abstract Background Circular RNAs (circRNAs) act as vital regulators of gene expression in a variety of cancers. However, the role of circRNAs in gastric cancer (GC) remains largely unexplored. Herein, we identified that circTMEM87A sponges miR-142-5p to promote GC progression through up-regulating ULK1 expression. Methods The expression of circTMEM87A in GC was determined by RNA sequencing and quantitative real-time PCR (qRT-PCR). The effects of knockdown or exogenous expression of circTMEM87A on GC cell phenotypes were evaluated both in vitro and in vivo. The interacting miRNA of circTMEM87A was predicted by bioinformatics and confirmed by RNA pull-down, dual-luciferase reporter assay and fluorescence in situ hybridization (FISH). The mechanism by which circTMEM87A/miR-142-5p/ULK1 axis promotes GC was determined by western blot, GFP/ Haixiao Wang, Guangli Sun and Penghui Xu are contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00535-020-01744-1) contains supplementary material, which is available to authorized users. & Zekuan Xu [email protected] 1
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
2
Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
3
Department of General Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China
mRFP-LC3 puncta analysis, transmission electron microscope (TEM). Results CircTMEM87A was dramatically elevated in GC tissues and cell lines, and high circTMEM87A expression was closely correlated with poor prognosis of GC patients. Knockdown of circTMEM87A suppressed cell growth, migration, invasion and induced apoptosis in vitro, as well as inhibited GC tumorigenicity and lung metastasis potential in vivo. Meanwhile, circTMEM87A overexpression had the opposite effects. Furthermore, we demonstrated that circTMEM87A could act as a sponge of miR142-5p to regulate ULK1 expression and GC progression. Conclusions Our findings suggest that circTMEM87A functions as an oncogene through the miR-142-5p/ULK1 axis in GC. CircTMEM87A might be a prognostic biomarker as well as a promising therapeutic target for GC. Keywords CircTMEM87A ULK1 Gastric cancer Proliferation Metastasis Abbreviations GC Gastric cancer circRNA Circular RNA qRT-PCR Quantitative real-time PCR FISH Fluorescence in situ hybridization RBP RNA binding protein miRNA MicroRNA 30 -U
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