MicroRNA-197 inhibits gastric cancer progression by directly targeting metadherin

Abstract

Gastric cancer is the fifth most frequent malignancy and the fourth most common cause of cancer‑associated mortality worldwide. MicroRNAs (miRNAs) are a group of small RNAs that regulate several cellular processes. In particular, a large number of miRNAs are involved in gastric cancer formation and progression. Thus, miRNAs may be considered as effective diagnostic biomarkers and therapeutic methods for gastric cancer. The aim of the current study was to detect miRNA (miR)‑197 expression in gastric cancer and to investigate its biological role and associated mechanism in gastric cancer. In the present study, miR‑197 expression was demonstrated to be considerably downregulated in gastric cancer tissues and cell lines. Its low expression level was associated with tumour size, invasive depth, tumour‑node‑metastasis staging and lymph node metastasis. High expression of miR‑197 inhibited tumour cell proliferation and invasion in vitro. Subsequently, metadherin (MTDH) was identified as a direct target gene of miR‑197 in gastric cancer, and this was confirmed by bioinformatics analysis, Dual‑luciferase reporter assay, reverse transcription quantitative polymerase chain reaction and western blot analysis. MTDH expression was upregulated in gastric cancer and was inversely correlated with miR‑197 expression levels. In addition, MTDH overexpression prevented the proliferation and inhibited invasion induced by miR‑197 overexpression. In addition, miR‑197 was demonstrated to regulate the phosphatase and tensin homolog (PTEN)/AKT signalling pathway in gastric cancer. The results of the present study suggested that miR‑197 serves a tumour‑suppressing role in human gastric carcinogenesis and progression by regulating the MTDH/PTEN/AKT signalling pathway. The miR‑197/MTDH axis may provide a novel effective therapeutic target for patients with gastric cancer.

<p>Long Noncoding RNA DLGAP1-AS1 Promotes the Aggressive Behavior of Gastric Cancer by Acting as a ceRNA for microRNA-628-5p and Raising Astrocyte Elevated Gene 1 Expression</p>

“…To elucidate the mechanism by which miR-628-5p suppressed GC progression, bioinformatics analysis was performed for miR-628-5p target prediction. AEG-1 was selected for further analysis as it is known to be closely associated with the progression of GC, [28][29][30][31][32][33][34][35]39 and the 3′-UTR of the AEG-1 mRNA was predicted to directly interact with miR-628-5p ( Figure 4G). To test this hypothesis, the luciferase reporter assay was carried out to evaluate the direct interaction between miR-628-5p and the 3′-UTR of AEG-1.…”

“…[28][29][30] Functionally, AEG-1 performes cancer-promoting actions in gastric carcinogenesis and cancer progression, and is involved in multiple aggressive phenotype. [31][32][33][34][35] Yet, as far as we know, there has been no study that has explored the issue of DLGAP1-AS1, miR-628-5p, and AEG-1 in GC. Herein, we also attempted to address the functions and associations between DLGAP1-AS1, miR-628-5p, and AEG-1 in GC.…”

MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2

“…In hepatocellular carcinoma, miR-197-3p was down-regulated in carcinoma tissues and its expression correlated with aggressive clinicopathological characteristics [ 20 ]. miR-197 depletion exerts an tumor suppressive effect on the progression of gastric cancer [ 31 ]. Moreover, miR-197 has been shown to be suppressed cell proliferation, migration, and invasion in glioblastoma [ 32 ].…”

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

“…MiR-197 is a direct metadherin (MTDH) inhibitor, which is a PTEN blocker. Thus, by suppressing MTDH, miR-197 activates PTEN and thereby inhibits the PI3K/AKT/mTOR signaling pathway [72].…”