Research Paper Volume 14, Issue 14 pp 5878—5894
MBD1/HDAC3-miR-5701-FGFR2 axis promotes the development of gastric cancer
- 1 Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi Province, P.R. China
- 2 Institute of Genetics and Developmental Biology, Translational Medicine Institute, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, P.R. China
- 3 Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710000, Shaanxi Province, P.R. China
- 4 Department of Hepatobiliary Chest Surgery, Shaanxi Provincial Corps Hospital of Chinese People’s Armed Police Force, Xi’an 710054, Shaanxi Province, P.R. China
- 5 School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, Zhejiang Province, P.R. China
- 6 Department of Cell Biology and Genetics, Medical School of Yan’an University, Yan’an 716000, Shaanxi Province, P.R. China
- 7 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, P.R. China
Received: November 17, 2021 Accepted: July 8, 2022 Published: July 22, 2022
https://doi.org/10.18632/aging.204190How to Cite
Copyright: © 2022 Zhao 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
Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide due to the lack of specific biomarkers for the early diagnosis and universal accepted therapy for advanced GC. Lower levels of miR-5701 were found in the GC tissue from the online sequencing data and confirmed in the GC tissues and GC cell lines. Overexpression of miR-5701 inhibited the proliferation and migration of GC cells and promoted the apoptosis of these cells. Bioinformatics analyses and luciferase assay showed that miR-5701 targeted FGFR2, which acted as an oncogene in GC. Nude mice with GC cells overexpressing miR-5701 exhibited smaller tumor sizes and less lung metastases. The miR-5701 expression was directly, transcriptionally inhibited by MBD1 together with HDAC3 by binding together to form a complex. Knocked down MBD1 or HDAC3 increased the miR-5701 expression. These results indicated the potential use of exogenously administered miR-5701 or agents that elevated endogenous miR-5701 to inhibit GC, improving the prognosis of patients with GC.
Abbreviations
miRNA: microRNA; DNMT3A: DNA methyltransferase 3A; TRD: transcriptional repression domain; FBS: Fetal Bovine Serum; siRNA: small interfering RNA; FGFR2: fibroblast growth factor receptor 2; TCGA: the cancer genome atlas; PMSF: Phenylmethanesulfonyl fluoride; TBST: TBS with Tween-20.