Research Paper Volume 13, Issue 16 pp 20302—20318

Regulation of follistatin-like 3 expression by miR-486-5p modulates gastric cancer cell proliferation, migration and tumor progression

Zhou-Tong Dai1, *, , Yuan Xiang1,2, *, , Xiao-Yu Zhang1, *, , Qi-Bei Zong1, , Qi-Fang Wu1, , You Huang1, , Chao Shen1, , Jia-Peng Li1, , Sreenivasan Ponnambalam3, , Xing-Hua Liao1, ,

  • 1 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei 430081, P.R. China
  • 2 Department of Medical Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, P.R. China
  • 3 School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
* Equal contribution

Received: March 11, 2021       Accepted: August 2, 2021       Published: August 23, 2021
How to Cite

Copyright: © 2021 Dai 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.


Cancer development and progression can be regulated by the levels of endogenous factors. Gastric cancer is an aggressive disease state with poor patient prognosis, needing the development of new diagnostics and therapeutic strategies. We investigated the close association between follistatin-like 3 (FSTL3) and different cancers, and focused on its role in gastric cancer cell function. Using cancer bioinformatics, we found that FSTL3 expression is elevated in a large majority of the 33 cancers we analyzed in publicly available cancer databases. Elevated levels of FSTL3 is associated with poor patient prognosis in gastric cancer. In a comparison of normal gastric epithelial cells and gastric cancer cell lines, FSTL3 expression was consistently elevated in gastric cancer cells. Overexpression of FSTL3 promoted gastric cancer cell viability, proliferation and migration. Conversely, FSTL3 knockdown inhibits these cellular processes. Using bioinformatics, we found that the FSTL3 mRNA has a potential binding site in the 3’-UTR for a small microRNA, miR-486-5p. Further bioinformatics revealed significant negative correlation between FSTL3 and miR-486-5p levels. Using luciferase reporter constructs, we provide evidence that the 3’UTR from the FSTL3 mRNA can confer downregulation in the presence of miR-486-5p. These studies lead us to conclude that FSTL3 has oncogenic properties and increased expression of this gene product promotes gastric cancer development and progression.


miRNA: microRNA; 3’-UTR: 3’untranslated region; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; PPI: Protein-protein interaction; STAD: stomach adenocarcinoma.