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

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.

Podocalyxin‐like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein

“…Here, we used the IHC method to detect PODXL expression in GC tissues and their corresponding NAT. A similar analysis performed by others also indicated that PODXL was a target gene of miR‐509‐3‐5p in GC patients and mediated tumor progression . Interestingly, our results also showed that PODXL was expressed more frequently in GC tissues compared with NAT.…”

“…A similar analysis performed by others also indicated that PODXL was a target gene of miR-509-3-5p in GC patients and mediated tumor progression. 24 Interestingly, our results also showed that PODXL was expressed more frequently in GC tis- Recent studies on the genomic landscape of gastric adenocarcinoma have identified several key signaling molecules, including epidermal growth factor receptor family (ErbB) members, vascular endothelial growth factor (VEGFR) receptor family members, and PI3K/Akt, NF-κB and MAPK/ERK pathway components, that were implicated in the molecular pathogenesis of GC. 37 For example, PI3Kp85α and p-AKT were expressed in gastric adenocarcinoma tissues, and targeting blockade of the PI3K pathway might inhibit GC growth and metastasis through downregulation of Ki-67 and MMP-2 expression.…”

“…This was the only evidence that PODXL served as a biomarker in breast cancer with good prognosis . To the best of our knowledge, there are few reports on the mechanism of PODXL in GC progression, although there are reports of the poor prognostic value of PODXL expression for GC patients . RUN and FYVE domain containing 1 (RUFY1) is a member of the RUFY family, whose members contain an N‐terminal RUN domain and a C‐terminal FYVE domain .…”

“…21 To the best of our knowledge, there are few reports on the mechanism of PODXL in GC progression, although there are reports of the poor prognostic value of PODXL expression for GC patients. [22][23][24] RUN and FYVE domain containing 1 (RUFY1) is a member of the RUFY family, whose members contain an N-terminal RUN domain and a C-terminal FYVE domain. 25,26 RUFY proteins are localized predominantly to early endosomes and participate in the regulation of diverse cellular processes.…”

A six‐microRNA signature to predict outcomes of patients with gastric cancer

“…These inconsistent results may be due to the different tumor types or microenvironments such as in vitro and in vivo . miRNA‐509‐3 has been previously identified as a tumor suppressor gene in lung cancer , ovarian cancer , hepatoma , leukemia , renal cell carcinoma , and GC . It was also an independent prognostic biomarker in GC patients.…”