miR-509-3-5P inhibits the invasion and lymphatic metastasis by targeting PODXL and serves as a novel prognostic indicator for gastric cancer

// Jing Zhang 1, * , Zhonglin Zhu 1, * , Jinxin Sheng 2, * , Zhilong Yu 1, * , Bin Yao 1 , Kejian Huang 1 , Lisheng Zhou 1 , Zhengjun Qiu 1 , Chen Huang 1 1 Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China 2 Department of General Surgery, Haimen People’s Hospital, Haimen 226100, Jiangsu province, China * These authors contributed equally to this work Correspondence to: Chen Huang, email: richard-hc@hotmail.com Keywords: miR-509-3-5p, PODXL, invasion, lymphatic metastasis, gastric cancer Received: February 17, 2017      Accepted: March 23, 2017      Published: April 04, 2017 ABSTRACT Background: Our study aimed to investigate the clinicopathological feature and prognostic role of miR-509-3-5P in gastric cancer, to determine the invasive and metastatic role of miR-509-3-5P in vitro and in vivo and to explore the molecular mechanism between miR-509-3-5P and PODXL. Results: Strikingly lower miR-509-3-5P expression was detected in gastric cancer tissues with advanced tumor stage, poor differentiation and advanced pT stage, and was regarded as an independent prognostic role for poor prognosis. MiR-509-3-5P expression was markedly down-regulated in gastric cancer cell lines and tissues comparing with normal gastric cell and adjacent normal tissues, respectively. Decreased expression of miR-509-3-5P promoted the colony, migration and invasion abilities of gastric cancer cells in vitro as well as tumorigenesis and lymph node metastasis in vivo . Based on the luciferase assay and tissue microarray, PODXL was regarded as a target gene of miR-509-3-5P. Materials and Methods: The expression of miR-509-3-5P in gastric cancer patients and its clinicopathological relationships as well as prognostic role was studied employing tissue microarray; qRT-PCR was applied to explore miR-509-3-5P expression in gastric cancer cell lines and samples. Moreover, public database was used to analyze the expression of miR-509-3-5P and PODXL. Functional and molecular mechanism experiments were performed in vitro and in vivo . Conclusions: Overexpression of miR-509-3-5P inhibits the invasion and metastasis of gastric cancer in vitro and in vivo , functioning as a tumor suppressor, by targeting PODXL. More importantly, miR-509-3-5P was downregulated in gastric cancer tissues and may serve as a novel prognostic indicator for gastric cancer.