MicroRNAs deregulation are common in human tumor progression. miR-1236-3p has been reported to function as tumor suppressor microRNA in various malignancies. The aim of this study was to demonstrate the downregulated expression of miR-1236-3p in gastric cancer (GC) tissues and cell lines, and clarify its biological function in GC. Real-time polymerase chain reaction was used to measure the mRNA level of miR-1236-3p in GC. Dual luciferase assay was used to demonstrate that MTA2 was one of the candidate target genes of miR-1236-3p. Western blots were utilized to detect the protein levels. Cell function assays were also performed to determine the function of miR-1236-3p in GC. miR-1236-3p expression, which was associated with lymph node metastasis, differentiation and clinical stage, was significantly reduced in GC tissues and cell lines. miR-1236-3p over-expression could inhibit GC cell proliferation, migration and invasion, and inhibition of miR-1236-3p expression had opposite effects. Furthermore, we demonstrated that MTA2 was a candidate target of miR-1236-3p, and miR-1236-3p over-expression significantly inhibited the process of epithelial–mesenchymal transition. We also found that miR-1236-3p could suppress the PI3K/Akt signaling pathway in GC cells. Our results suggest that miR-1236-3p functions as a tumor suppressor in GC and could be a promising therapeutic target for GC.

Currently, cancer-related competing endogenous RNA (ceRNA) networks are attracting significant interest. As long noncoding RNA ZEB1-AS1 has been reported to function as an oncogene due to sponging microRNAs (miRNAs) in several cancers, we hypothesized that it could interact with specific miRNAs to form regulatory networks and facilitate the growth of gastric cancer (GC). MiRNAs interacting with ZEB1-AS1 were screened for and selected by bioinformatics analysis. Overexpression or repression of ZEB1-AS1 was performed to determine whether it could regulate selected miRNAs. Quantitative real-time polymerase chain reactions (qPCR) validated the expression profiles of ZEB1-AS1 and miR-149-3p in GC cell lines and tissue. Statistical analysis determined the clinical significance of ZEB1-AS1 in relation to miR-149-3p. Cell counting, wound healing and transwell assays were performed to assess cell proliferation, migration and invasion. A luciferase reporter assay was utilized to confirm the putative miR-149-3p-binding sites in ZEB1-AS1. Briefly, bioinformatics analysis inferred that ZEB1-AS1 interacts with miR-204, miR-610, and miR-149. Gain- or loss-of function assays suggested that ZEB1-AS1 negatively regulates miR-149-3p, miR-204-5p and miR-610 in GC cells. Validated by qPCR, ZEB1-AS1 was up-regulated and miR-149-3p down-regulated in GC cells and tissue. Data analyses indicated that ZEB1-AS1 and miR-149-3p are associated with the independent diagnosis and prognosis of GC. Functional assays support the theory that miR-149-3p hinders GC proliferation, migration and invasion, whereas its overexpression abrogates the corresponding effects induced by ZEB1-AS1. Lastly, dissection of the molecular mechanisms involved indicated that ZEB1-AS1 can regulate GC partly via a ZEB1-AS1/miR-149-3p axis. ZEB1-AS1 can interact with specific miRNAs, forming a miRNA-mediated ceRNA network and promoting GC progress, partly through a ZEB1-AS1/miR-149-3p axis.

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