Abstract
Numerous studies have shown drug resistance of gastric cancer cells could be modulated by abnormal expression of microRNAs. Cisplatin (DDP) is one of the most commonly used drugs for chemotherapy of gastric cancer. In this study, the potential function of miR-125b on DDP resistance in gastric cancer cells was investigated. Sixteen miRNAs significantly differential expressed in gastric tumor tissues and adjacent tissues were characterized and their corresponding putative target genes were also screened. MiR-125b was selected as our focus for its evident down-regulated expression among candidate genes. Real-time polymerase chain reaction assay indicated that miR-125b was significantly down-regulated in gastric cancer tissues and various cell lines. HER2 was identified as a target gene of miR-125b by dual luciferase reporter assay and Western blot. Moreover, miR-125b overexpression inhibited not only the proliferation, migration, and invasion abilities of HGC-27 and MGC-803 cells, but also in vivo tumor growth of MGC-803 cells by an intratumoral delivery approach. Notably, we observed up-regulated miR-125b contributed to the chemosensitivity of DDP in HGC-27 and MGC-803 cells at different concentrations and also possessed sensibilization for DDP at different times. MiR-125b expression was found to be related to lymph node metastasis, HER2 expression and overall survival of patients through correlation analysis. Collectively, these results indicate miR-125b may regulate DDP resistance as a promising therapeutic target for gastric cancer treatment in future.
Highlights
Gastric cancer is one of the most common malignant diseases and the second leading cause of cancer-related deaths worldwide, especially in the Asian countries [1]
We had characterized sixteen miRNAs significantly differential expressed in tumor tissues and adjacent tissues based on fold change more than 2
T-test was used to analyze the difference between gastric cancer tissues and matched normal tissues according to their corresponding ΔCt values of miR-125b expression
Summary
Gastric cancer is one of the most common malignant diseases and the second leading cause of cancer-related deaths worldwide, especially in the Asian countries [1]. Abnormal expression caused by miRNA regulation could lead to the pathogenesis and development of various tumors [9]. Numerous studies indicate that miR-21 is implicated in colorectal cancer [10], hepatocellular carcinoma [11], gastric cancer [12] and other cancers. Another miRNA, miR-125b, has been shown to exert abnormal expression in a variety of tumors and its effects vary with different tumors [13, 14]. MiR-125b overexpression may increase proliferation but decrease apoptosis [15]. The mechanism of miR-125b and its impact on the chemosensitivity in gastric cancer remains largely unknown
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