MicroRNA-454 inhibits the malignant biological behaviours of gastric cancer cells by directly targeting mitogen-activated protein kinase 1

Abstract

Gastric cancer (GC) is the fifth most commonly diagnosed malignant disease and the third leading cause of cancer-related deaths worldwide. Recently, numerous microRNAs (miRNAs) have been determined to contribute to GC initiation and progression, suggesting that miRNAs may be developed as effective diagnostic and prognostic molecular biomarkers and can be investigated as therapeutic targets for patients with this disease. Therefore, further investigation of the miRNAs involved in GC development represents an opportunity to improve the prognosis of GC patients. miRNA-454 (miR-454) is abnormally expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanism of miR-454 in GC remain unclear and require further investigation. In the present study, we assessed miR-454 expression in GC tissues and cell lines. We also explored the effects of miR-454 on the biological behaviours of tumour cells and the underlying molecular mechanisms of miR-454. The results revealed that miR-454 was significantly downregulated in GC tissues and cell lines. Low miR-454 expression was positively associated with lymph node metastasis, invasive depth and TNM stage. Additionally, upregulation of miR-454 inhibited cell proliferation and invasion and induced the apoptosis of the GC cells. Subsequently, mitogen-activated protein kinase 1 (MAPK1) was identified as a direct target of miR-454. MAPK1 was upregulated in GC tissues and was found to be negatively correlated with the miR-454 expression level. Downregulation of MAPK1 also suppressed GC cell proliferation and invasion and increased apoptosis, thereby resembling the suppressive effects of miR-454 overexpression in GC. Moreover, upregulation of MAPK1 reversed the tumour-suppressive effects of miR-454 in GC. Collectively, our data demonstrated that miR-454 may play tumour-suppressing roles in GC through the regulation of MAPK1, suggesting that miR-454 may be a novel biomarker and therapeutic target for patients with this disease.