Abstract
BackgroundOur 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.ResultsStrikingly 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 MethodsThe 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.ConclusionsOverexpression 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.
Highlights
Gastric cancer (GC), one of the malignant cancer in digestive system, accounts for about 7% of all cancer cases and 9% of all cancer-related death worldwide [1]
MiRNA microarray was applied to detect the potential differential expressed miRNAs in 10 tissues of GC with N0 and 10 tissues of GC with N3, we found that miR-509-3-5P, miR1180-3P, miR-936 and so forth were downregulated in N3 group (Figure 1A), which might be associated with lymph node metastasis
We found that miR-509-3-5P was downregulated in fresh tissues of GC (Figure 1B), and the decreased miR-5093-5P expression was correlated with advanced clinicopathologic stage (UICC stage), but associated with poor differentiation, tumor stage(pT stage), lymph node metastasis
Summary
Gastric cancer (GC), one of the malignant cancer in digestive system, accounts for about 7% of all cancer cases and 9% of all cancer-related death worldwide [1]. The critical roles of miRNAs involved in tumor metastasis, which was a pivotal step for poor prognosis, was further supported by various studies [11, 12]. A self-assembled cell microarray was applied to detect the specific miRNAs mediating GC metastasis, and the final results revealed that miR-451, downregulated in human GC specimens, could suppress the metastasis of GC via targeting ERK2 [13]. It was found by Tsai et al that decreased expressions of miR-26b in fresh GC tissues were associated with advanced clinicopathological stage, and correlated with distant metastasis. 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
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