Effect of miR-4270 on Tumorigenicity in Gastric Cancer Stem Cells via the Wnt Signaling Pathway.

Background: Cancer stem cells and miRNAs are the most important factors in the tumorigenicity of cancers. So, we evaluated the properties of gastric cancer stem-like cells (GCSCs) under treatment using a hsa-miR-4270 inhibitor and a mimic. Materials and Methods: We isolated GCSCs from the MKN-45 cell line using a non-adherence surface method. Then, GCSCs were treated with hsa-miR-4270 inhibitor/mimic with different concentrations, and the cell proliferation was measured with the MTT assay to find the suitable concentration of inhibitor/mimic for following experiments. Apoptosis, angiogenesis, and metastasis were evaluated by DNA laddering, tube formation, zymography and Transwell assay, respectively. Transcription of the genes in Wnt1 signaling was measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Protein levels of Wnt1, CTNNB1P1, and SMARCD1 were evaluated by western blotting, and interactions between genes involved in our study were examined by STRING and Gene mania tools. Results: The results showed that the hsa-miR-4270 inhibitor declined cell proliferation, MMP activity, migration, and angiogenesis, and induced apoptosis. However, the hsa-miR-4270 mimic had opposite effects on those cell functions. The results of the effects of hsa-miR-4270 inhibitor/mimic on the Wnt1 signaling pathway revealed that the arrest of miR-4270 could inhibit the canonical Wnt1 signaling pathway. Conclusions: In summary, hsa-miR-4270 is an oncomir in the tumorigenicity of GC stem cells, which may be considered an appropriate candidate for GC treatment.