Open Access

ARTICLE

Tumor-Suppressive MicroRNA-708 Targets Notch1 to Suppress Cell Proliferation and Invasion in Gastric Cancer

Xuyan Li^*1, Xuanfang Zhong^†1, Xiuhua Pan^‡, Yan Ji^§

* Clinical Laboratory Central, Huizhou Central People’s Hospital, Guangdong, P.R. China
† Department of Digestion, Huizhou Central People’s Hospital, Guangdong, P.R. China
‡ Department of Radiotherapy, Huizhou Central People’s Hospital, Guangdong, P.R. China
§ Department of Prenatal Diagnosis, Huizhou Central People’s Hospital, Guangdong, P.R. China
1 These authors provided equal contribution to this work.

Oncology Research 2018, 26(9), 1317-1326. https://doi.org/10.3727/096504018X15179680859017

Abstract

Growing evidence has demonstrated that numerous microRNAs (miRNAs) may participate in the regulation of gastric carcinogenesis and progression. This phenomenon suggests that gastric cancer-related miRNAs can be identified as effective therapeutic targets for this disease. miRNA-708 (miR-708) has recently been reported to be aberrantly expressed in several types of cancer and contribute to carcinogenesis and progression. However, the expression level, biological roles, and underlying mechanisms of miR-708 in gastric cancer are poorly understood. Here we found that miR-708 was downregulated in gastric cancer tissues and cell lines. Downregulated miR-708 expression was significantly associated with lymphatic metastasis, invasive depth, and TNM stage. Further investigation indicated that ectopic expression of miR-708 prohibited cell proliferation and invasion in gastric cancer. Bioinformatics analysis showed that Notch1 was a potential target of miR-708. Notch1 was further confirmed as a direct target gene of miR-708 in gastric cancer by dual-luciferase reporter assay, reverse transcription quantitative polymerase chain reaction, and Western blot analysis. Furthermore, an inverse association was found between miR-708 and Notch1 mRNA levels in gastric cancer tissues. In addition, restored Notch1 expression rescued the inhibitory effects on gastric cancer cell proliferation and invasion induced by miR-708 overexpression. Our findings highlight the tumor-suppressive roles of miR-708 in gastric cancer and suggest that miR-708 may be investigated as a novel target for gastric cancer treatment.

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