Abstract
Many gene expressions changed during the development of gastric cancer, and non-coding RNAs including microRNAs (miRNAs) have been found to regulate cancer progression by participating in the process of tumor cell growth, migration, invasion and apoptosis. Our previous study has identified 29 miRNAs that are highly expressed in gastric cancer stem cells. One of these miRNAs, miR-1915-3p, has shown great potential as a diagnostic and prognostic biomarker for the cancers in liver, colon and thyroid, as well as in immune and kidney diseases. Herein, we found that miR-1915-3p exhibited low expression level in differentiated gastric cancer cell lines and gastric cancer tissues. It was found that the miR-1915-3p inhibited the growth of gastric cancer cells and thus promoted cell apoptosis. We discovered that the expressions of miR-1915-3p were significantly correlated to the lymph node metastasis and overall survival of patients with gastric cancer. Further study showed that there was a negative correlation between miR-1915-3p and Bcl-2 (B cell lymphoma/leukemia-2) expression, suggesting that Bcl-2 was a target gene of miR-1915-3p. Hence, miR-1915-3p possibly contributes to the development and progression of gastric cancer by inhibiting the anti-apoptotic protein Bcl-2. The finding provides a potential therapeutic strategy for gastric cancer.
Highlights
Gastric cancer is one of the most common malignant tumors of digestive tract and is the leading cause of cancer-related death worldwide [1]
Previous miRNA expression profile study has identified 29 miRNAs, such as hsa-mir-338-5p, hsa-mir-3178 and mir-1915-3p that are highly expressed in gastric cancer stem cells [11]. miR-1915-3p is highly expressed in thyroid cancer [12], attenuated oxidative stress responses in hepatocellular carcinoma [13], and associated with immune cell proliferation and senescence [14]
Combining the data from TargetScan and miRDB databases, gene ontology, enrichment analysis and pathway analysis revealed that differentially expressed miRNAs are associated with tumor formation and apoptosis-related genes, including Bcl-2 (B cell lymphoma/leukemia-2) family, which is generally recognized as one of the key factors involved in cell apoptosis [15,16]
Summary
Gastric cancer is one of the most common malignant tumors of digestive tract and is the leading cause of cancer-related death worldwide [1]. Numerous studies reported that the abnormal expression of microRNAs (miRNAs) have been found in some cancer patients and could serve as biomarkers for early detection, treatment and prognosis of gastric cancer [4,5,6,7,8,9,10]. Previous miRNA expression profile study has identified 29 miRNAs, such as hsa-mir-338-5p, hsa-mir-3178 and mir-1915-3p that are highly expressed in gastric cancer stem cells [11]. Combining the data from TargetScan and miRDB databases, gene ontology, enrichment analysis and pathway analysis revealed that differentially expressed miRNAs are associated with tumor formation and apoptosis-related genes, including Bcl-2 (B cell lymphoma/leukemia-2) family, which is generally recognized as one of the key factors involved in cell apoptosis [15,16]
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