Increased expression of miR‐146a, miR‐10b, and miR‐21 in cancer stem‐like gastro‐spheres

BACKGROUND: Gastric cancer remains one of the leading causes of cancer-associated mortalities globally. Accumulating evidence support the presence of gastric cancer stem cells (CSCs) and their role in the pathogenesis and therapeutic challenges of gastric cancer. MicroRNAs (miRNAs) may be influenced by the cellular differentiative state and as critical regulators of the cellular fate in development and cancer, can modulate the behavior of CSCs too. Here, we aimed to investigate the expression relevance of three prognostic miRNAs (miR-21, miR-10b, and miR-146a) in CSCs of AGS and MKN-45 gastric cancer cell lines. METHODS: Serial sphere-forming assay in serum-free culture medium was used to enrich the cellular population with stem-like properties. Gastro-spheres were characterized by evaluating the stemness gene expression, clonogenicity, and resistance to docetaxel and cisplatin in comparison with their parental cells. The expression level of miRNAs in gastro-spheres and their parental cells was measured using quantitative reverse transcription polymerase chain reaction. RESULTS: Gastro-spheres from both cell lines exhibit stem-like properties: upregulated stemness associated genes (P < 0.05), more colonogenicity and more resistance to docetaxel (P < 0.05). MKN-45 gastro-spheres exhibited upregulated expression of miR-21 (1.8-folds), miR-10b (1.34-folds) and miR-146a (4.8-folds; P < 0.05) compared with the parental cells. AGS-derived gastro-spheres showed upregulation of miR-21 (4.7-folds; P < 0.01), miR-10b (15.2-folds; P < 0.001) and miR-146a (39.3-folds; P < 0.05). CONCLUSION: Our data exhibited upregulation of miR-21, miR-10b, and miR-146a in the stem-like gastro-spheres; however; their function in gastric CSCs remains to be verified by further experiments.