Abstract
Recent evidences demonstrate that dysregulated expression of microRNA-320d (miR-320d) has been associated with several cancer development and progression. However the effect of miR-320d on gastric cardiac adenocarcinoma (GCA) and the association of miR-320d with its potential gene target FoxM1 remain unclear. Here, we evaluated expression profile of miR-320d and FoxM1 in 60 human GCA tissues and GCA cell lines (OE-19 and SK-GT2). Immunohistochemistry, qualitative PCR and western-blotting were performed in GCA tissues to detect the expression level of miR-320d and FoxM1. CCK-8, transwell, wound-healing assays, and in vivo experiments were conducted using GCA cells that treated with miR-320d mimics or inhibitors to evaluate the biological functions of miR-320d. Luciferase reporter assay was conducted to confirm possible binding sites of FoxM1 for miR-320d. Compared with paired non-cancerous tissues, it showed that miR-320d expression was significantly decreased in GCA specimens (P < 0.0001), while FoxM1 was significantly upregulated in GCA tissues (P < 0.0001). Modulating miR-320d function by transfection of miR-320 mimics or inhibitor led to inhibition or promotion of GCA cell proliferation and invasion, thus regulating tumor progression in GCA-tumor bearing mice. The mechanism analysis of miR-320d/FoxM1 showed that FoxM1 has two miR-320d binding sites in its 3′-untranslated region (3′-UTR), that contributes to regulation of the cell biological behaviors. Taken together, our data suggested that miR-320d acts as a tumor suppressor in GCA by directly targeting FoxM1 and thus potentially serves as a biomarker for anti-GCA therapy in GCA patients.
Highlights
According to nationwide statistics of cancer incidence and mortality in China, gastric cancer ranks as the second prevalent cancer type, and the third most common cause of death [1]
MiR‐320d is negatively correlated with Forkhead box M1 (FoxM1) in gastric cardia adenocarcinoma (GCA) tissues, both are associated with prognosis of GCA patients Firstly, we aimed to determine the miR-320d’s target genes and the binding sites
Based on the available online bioinformatics websites, we found that there are two potential binding sites between the FoxM1 3′-untranslated region (3′-UTR) and miR-320d, and the context score of these sites are high, which suggested FoxM1 may serve as a potential target gene for miR-320d
Summary
According to nationwide statistics of cancer incidence and mortality in China, gastric cancer ranks as the second prevalent cancer type, and the third most common cause of death [1]. Unlike other types of gastric cancer, gastric cardia adenocarcinoma (GCA) is a special aggressive cancer and has its own epidemiological and. Chen et al Cell Biosci (2020) 10:80 crucial role throughout the physiological processes of cells, including development, metabolism, proliferation, differentiation, and apoptosis [14, 15]. More than 1000 miRNAs are reported in encoding in the human genome. Among these revealed miRNAs, microRNA-320d (miR-320d), a member of miR-320 family, has been reported to be involved in different malignant tumors, including large B cell lymphoma [14], colon cancer [15], renal cell carcinoma [16]. Studies focusing on the role and mechanism of miR-320d in the progression and development of GCA are still lacking
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