OncoTargets and Therapy (Mar 2020)
miR-26a-5p Inhibit Gastric Cancer Cell Proliferation and Invasion Through Mediated Wnt5a
Abstract
Yu Li,1,* Peng Wang,1,* Lei-Lei Wu,2 Jun Yan,1 Xue-Ying Pang,1 Song-Jiang Liu1 1Department of Oncology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, People’s Republic of China; 2School of Pharmaceutical Sciences, Mudanjiang Medical University, Mudanjiang 157011, Heilongjiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song-Jiang LiuDepartment of Oncology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 26, Heping Road, Harbin 150040, Heilongjiang Province, People’s Republic of ChinaTel +86-13796228787Email [email protected]: Gastric cancer (GC) is a malignant disease of digestive tract. Clinically, radiation therapy is widely applied in treating GC, while with undesirable outcome due to tumor re-proliferation and recurrence and metastasis after radiation. Therefore, it is crucial to explore potential molecular mechanisms to develop therapeutic strategies. The present study found that miR-26a-5p has low expression in GC patients and could regulate Wnt5a to inhibit tumor growth, which was a potential therapeutic target for GC. To explore the expression and related mechanism of miR-26a-5p and Wnt5a in GC.Patients and Methods: MiR-26a-5p and Wnt5a were extracted from the transcriptome data of GC downloaded from TCGA database for analysis. The expression levels of miR-26a-5p and Wnt5a in patients’ tissues and serum were detected by qRT-PCR, and their correlation with patients’ pathological data and survival was analyzed. In addition, miR-26a-5p and Wnt5a overexpression and inhibition vectors were transfected into cells to observe the effects on the proliferation, invasion and apoptosis of GC cells. The relationship between miR-26a-5p and Wnt5a was analyzed by dual luciferase report.Results: The database and clinical samples showed that miR-26a-5p level was low while Wnt5a was high in GC. MiR-26a-5p level decreased in patients with stage III+IV, lymphatic metastasis and tumor ≥ 3cm, and Wnt5a was contrary to that of the miR-26a-5p, with diagnostic value. Overexpressed miR-26a-5p and inhibited Wnt5a enhanced apoptosis, decreased proliferation and invasion, reduced Bcl-2 and β-catenin proteins, and elevated Caspase 3, E-cadherin and Bax proteins, while inhibited miR-26a-5p and over-expressed Wnt5a showed the opposite results. Dual luciferase report confirmed that miR-26a-5p targeted to regulate Wnt5a, and rescue experiments found that these effects could be counteracted by reducing miR-26a-5p level.Conclusion: Overexpressed miR-26a-5p can inhibit Wnt5a expression, promote cell apoptosis, and suppress cell proliferation and invasion in GC.Keywords: TCGA, miR-26a-5p, Wnt5a, gastric cancer, survival, diagnosis
