Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1.

摘要: MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, they have been revealed crucial modulators in progression. However, our understanding of their roles gastric carcinoma (GC) metastasis is limited. Here, we aimed identify novel miRNAs involved GC and explored regulatory mechanisms significance GC. The microRNA expression profiles tumors at different stages statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset TCGA. Using above method, miR-4521 was picked out for further study. tissues examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) situ hybridization (ISH). Highly lowly invasive cell sublines established a repetitive transwell assay. Gain-of-function loss-of-function analyses performed investigate functions its upstream downstream vitro vivo. Moreover, investigated role mouse xenograft model. In this study, found that downregulated with adjacent normal downregulation positively correlated advanced clinical stage, status poor patient prognosis. Functional experiments inhibited invasion Further studies showed hypoxia repressed via inducing ETS1 mitigated hypoxia-mediated metastasis, while inactivated AKT/GSK3β/Snai1 pathway targeting IGF2 FOXM1, thereby inhibiting epithelial-mesenchymal transition (EMT) process metastasis. addition, demonstrated delivery synthetic suppressed progression Our results suggest an important regulating hypoxic response cells well miRNA