4.7 Article

Circular RNA TMEM87A promotes cell proliferation and metastasis of gastric cancer by elevating ULK1 via sponging miR-142-5p

Journal

JOURNAL OF GASTROENTEROLOGY
Volume 56, Issue 2, Pages 125-138

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s00535-020-01744-1

Keywords

CircTMEM87A; ULK1; Gastric cancer; Proliferation; Metastasis

Funding

  1. National Natural Science Foundation of China [81871946, 81802917, 81902515]
  2. Primary Research & Development Plan of Jiangsu Province [BE2016786]
  3. Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU
  4. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) [JX10231801]
  5. Jiangsu Key Medical Discipline (General Surgery) [ZDXKA2016005]
  6. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University

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Our study revealed that circTMEM87A is upregulated in GC tissues and cell lines, and its high expression is associated with poor prognosis in GC patients. CircTMEM87A functions as an oncogene by sponging miR-142-5p to regulate ULK1 expression and promote GC progression, indicating its potential as a prognostic biomarker and therapeutic target in GC.
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/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 miR-142-5p 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.

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