miR-767-5p negatively regulates HIF3A to regulate proliferation and EMT in gastric cancer through the PI3K/AKT pathway

BACKGROUND: Gastric cancer (GC) is commonly found among gastrointestinal tract cancers, and it often exhibits a poor prognosis. MiRNA-767-5p, a microRNA (miRNA), has been related to the progression and prognosis of numerous human cancers. Currently, the level of miR-767-5p expression and its function have not been thoroughly investigated in GC.METHODS: We examined miR-767-5p and target gene hypoxia-inducible factor-3α (HIF3A) mRNA expression in GC and normal tissues, and also in GES-1 cells, N87 cells, and GAS cells using qRT-PCR. We used MTT, plate cloning, and EdU staining assays to measure the variations in the biological properties of GC cells. The Epithelial-mesenchymal transition (EMT) process and the effects of miR-767-5p and HIF3A on the PI3K/AKT signaling pathway in GC cells were analyzed through Western blotting.RESULTS: MiR-767-5p exhibited a high level of expression in GC. Inhibitors of miR-767-5p hindered the proliferation, clonal formation capability, and EMT process in GC cells. In addition, there was a negative correlation between miR-767-5p and HIF3A mRNA expression. The silencing of HIF3A boosted proliferation and colony formation abilities in GC cells, and partially offset the suppression inflicted by miR-767-5p inhibitors on these cells. Silencing miR-767-5p impeded the PI3K/AKT pathway, whereas silencing HIF3A activated this pathway. The use of PI3K/AKT pathway agonists amplified the effects of HIF3A silencing, which could further enhance GC cell proliferation and EMT, as opposed to the effects of PI3K/AKT pathway inhibitors.CONCLUSIONS: MiR-767-5p negatively regulates HIF3A and is involved in the proliferation and EMT process via the PI3K/AKT signaling pathway in GC.