Abstract
Purpose Gastric cancer is one of the most common cancers in the world. miRNAs play an important role in regulating gene expression by binding with 3′-UTR of the target gene. The aim of this study was to investigate the function of miRNA-149 and FOXC1 in gastric cancer. Patients and Methods. qRT-PCR was used to detect the expression of miRNA-149 and FOXC1 in gastric cancer tissues and cells. Human gastric cancer cell lines AGS and MKN28 were cultured and transfected with miR-149 overexpression plasmid and its control or FOXC1 siRNA and its control. The MTT, colony formation, flow cytometry, wound healing, transwell, and western blotting were performed to examine the function of miRNA-149 and FOXC1 in the development of gastric cancer. What is more, dual-luciferase assay and western blotting were used to demonstrated the relationship between miRNA-149 and FOXC1. Results miRNA-149 was underexpressed in gastric cancer tissues and cells, while overexpression of miRNA-149 promoted cell apoptosis, retarded cell cycle, and inhibited proliferation and migration in AGS and MKN28 cells. In addition, we showed that miRNA-149 targeted FOXC1. What is more, FOXC1 was highly expressed in gastric cancer tissues and cells; the silencing of FOXC1 inhibited the biological function of AGS and MKN28 cells. Conclusion miRNA-149 inhibits the biological behavior of gastric cancer by targeting FOXC1, providing a promising target in the treatment of human gastric cancer.
Highlights
Gastric cancer is a highly recurrent malignancy
We investigated the inhibitory effects of miR-149 on the biological functions of gastric cancer cells by targeting FOXC1
High expression of miR103a-3p in gastric cancer tissue promotes cell growth causing the cell cycle to transition from the S phase to G2/M phase and plays the role of an oncogene [23]. miR-34a is downregulated in gastric cancer and targets PDGFR and MET through the PI3K/Akt pathway to inhibit tumorigenesis of gastric cancer [24]. miR-149 is abnormally expressed in several malignant tumors and can be used as an oncogene or tumor suppressor gene to regulate the biological behavior of tumor cells. miR-149 inhibits the proliferation and migration of hepatocellular carcinoma cells and hepatocarcinogenesis by impeding the NF-κB and STAT3 signaling pathways [14]
Summary
Gastric cancer is a highly recurrent malignancy. The incidence rate of gastric cancer is fifth in the world, and the mortality rate is third, second only to lung cancer and colorectal cancer [1]. The detection rate of early gastric cancer is low and lacks specificity. In light of the advancements in tumor biology and molecular technology, further research into the molecular mechanism involved in gastric cancer and identification of biomarkers with high specificity and good targeting [3] is of great significance for the diagnosis and treatment of this condition. MicroRNAs (miRNAs) are noncoding RNAs of approximately 22 nucleotides, which are key regulators of gene expression [4]. 3% of the human genome codes for miRNA sequences, which can suppress gene expression by mediating translational repression [5]
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