1. MicroRNA-34A inhibits the growth, invasion and metastasis of gastric cancer by targeting PDGFR and MET expression
- Author
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Jin‑Jun Guo, Yang Peng, Yan‑Min Liu, and Xiao‑Ling Wu
- Subjects
Male ,Expression of Concern ,Receptor, Platelet-Derived Growth Factor alpha ,PDGFR ,Biophysics ,lcsh:Life ,lcsh:QR1-502 ,Down-Regulation ,Biochemistry ,Receptor tyrosine kinase ,lcsh:Microbiology ,Metastasis ,Receptor, Platelet-Derived Growth Factor beta ,Phosphatidylinositol 3-Kinases ,Growth factor receptor ,Cell Movement ,Stomach Neoplasms ,Cell Line, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,RNA, Neoplasm ,Phosphorylation ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,biology ,gastric cancer ,Cancer ,Cell Biology ,Proto-Oncogene Proteins c-met ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,lcsh:QH501-531 ,MicroRNA 34a ,embryonic structures ,Cancer research ,biology.protein ,cardiovascular system ,MET ,Female ,Proto-Oncogene Proteins c-akt ,Platelet-derived growth factor receptor ,miR-34a ,Signal Transduction - Abstract
Within the family of RTKs (receptor tyrosine kinases), PDGFR (platelet-derived growth factor receptor) has been implicated in carcinogenesis and tumour development. miRNAs (microRNAs), which can target the mRNAs (messenger RNAs) of cancer-associated genes, are abnormally expressed in various cancers. In this study, our aim was to identify the miRNAs that target PDGFR-α/β and to study the functions of these miRNAs. miR-34a was predicted to target PDGFR, and luciferase reporter assays showed that miR-34a could directly target PDGFR. Meanwhile, we found that miR-34a was down-regulated in gastric cancer tissues and was associated with metastasis. Our findings showed that miR-34a could inhibit gastric cancer cell migration, invasion and proliferation, but these tumourigenic properties were only partially restored when PDGFR-α/β was overexpressed. In subsequent experiments, we found that the overexpression of both PDGFR and MET could completely restore the gastric cancer tumourigenic properties. Moreover, the cancer-associated cell signalling pathway was studied, and we found that miR-34a could inhibit Akt [PKB (protein kinase B)] phosphorylation, which was restored by the overexpression of both PDGFR and MET. In conclusion, miR-34a may act as a potential tumour suppressor in gastric cancer and is associated with the mechanisms of gastric cancer metastasis; miR-34a can inhibit gastric cancer tumourigenesis by targeting PDGFR and MET through the PI3K (phosphoinositide 3-kinase)/Akt pathway.
- Published
- 2014