H19 Rises in Gastric Cancer and Exerts a Tumor-Promoting Function via miR-138/E2F2 Axis

Jingrong Yu, 1,* Cheng Fang, 2,* Ziyue Zhang, 2 Guifang Zhang, 3 Lihong Shi, 4 Jiayi Qian, 5 Jianping Xiong 6 1Department of Oncology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330003, People’s Republic of China; 2Department of Oncology, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 4Department of Gynecology and Pediatrics, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 5Department of Ultrasound Electrophysiology, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 6Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianping XiongDepartment of Oncology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Street, Nanchang, Jiangxi Province 330006, People’s Republic of ChinaTel +86-13265847851Email jpxiong@medmail.comPurpose: The aim of this paper was to investigate H19 expression in gastric cancer (GC) and its effects on the biological behavior of gastric cancer cells (GCCs), and at exploring its potential mechanism.Methods: H19 expression in the patients’ tissues and serum was detected, and the correlation of the expression with the patients’ pathological data and survival rate was analyzed. Overexpression or inhibitory vectors of H19, microRNA-138 (miR-138) and E2F2 were constructed and transfected into GCCs to observe their effects on the cells’ proliferation, invasion and apoptosis.Results: H19 rose in GC and was higher in GC patients with a tumor size ≥ 5 cm, high stages (III+IV) and lymph node metastasis. High H19 expression was associated with the poorer survival rate of the patients, so serum H19 had a certain diagnostic value for GC. H19 knockdown could inhibit GCCs to proliferate and invade and induce their apoptosis. miR-138 can be used as the target gene of H19, and E2F2 can be negatively regulated by this miR, so miR-138 knockdown or E2F2 upregulation can weaken GCCs’ biological behavior changes that were caused by H19 knockdown.Conclusion: H19 can be used as a biological indicator for diagnosing GC and predicting patients’ poor prognosis. Additionally, it promotes GCCs to proliferate and invade through miR-138/E2F2 axis.Keywords: H19, miR-138, E2F2, gastric cancer