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Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non‐coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC....

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Autores principales: Zhao, Xiaohui, Liu, Yimin, Li, Zhihua, Zheng, Shangyou, Wang, Zairui, Li, Wenzhu, Bi, Zhuofei, Li, Liting, Jiang, Yanhui, Luo, Yuming, Lin, Qing, Fu, Zhiqiang, Rufu, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742682/
https://www.ncbi.nlm.nih.gov/pubmed/28984028
http://dx.doi.org/10.1111/jcmm.13351
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author Zhao, Xiaohui
Liu, Yimin
Li, Zhihua
Zheng, Shangyou
Wang, Zairui
Li, Wenzhu
Bi, Zhuofei
Li, Liting
Jiang, Yanhui
Luo, Yuming
Lin, Qing
Fu, Zhiqiang
Rufu, Chen
author_facet Zhao, Xiaohui
Liu, Yimin
Li, Zhihua
Zheng, Shangyou
Wang, Zairui
Li, Wenzhu
Bi, Zhuofei
Li, Liting
Jiang, Yanhui
Luo, Yuming
Lin, Qing
Fu, Zhiqiang
Rufu, Chen
author_sort Zhao, Xiaohui
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non‐coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC. Linc00511 levels in PDAC tissue specimens and cell lines were examined by quantitative real‐time PCR. Corresponding adjacent non‐neoplastic tissues were used as controls. The function of linc00511 in PDAC cell lines was determined by RNA interference approach in vitro and in vivo. Fluorescence in situ hybridization (FISH) was used to characterize linc00511 expression in PDAC cells. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were obtained from bioinformatic analysis, luciferase assays and RIP assays. The association between the linc00511/hsa‐miR29b‐3p axis and VEGFA was verified by Western blotting assay. Immunohistochemistry was performed to evaluate the expression of VEGFA in PDAC samples. The aberrant up‐regulation of linc00511 was detected in PDAC cell lines and patient specimens compared with controls. An increase in linc00511 expression indicates the adverse clinical pathological characteristics and poor prognosis. Functionally, linc00511 depletion in PDAC cells decreased proliferation, migration, invasion and endothelial tube formation. Mechanistically, linc00511 could up‐regulate VEGFA via its competing endogenous RNA (ceRNA) activity on hsa‐miR‐29b‐3p. In summary, our results define an important axis controlling proliferation, invasion and tumour angiogenesis in PDAC. Linc00511 is a novel lncRNA that plays a significant regulatory role in the pathogenesis and progression of PDAC. Thus, Linc00511 represents a new prognostic biomarker to predict clinical outcome of PDAC patients after surgery and may serve as a potential therapeutic target for PDAC treatment.
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spelling pubmed-57426822018-01-04 Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma Zhao, Xiaohui Liu, Yimin Li, Zhihua Zheng, Shangyou Wang, Zairui Li, Wenzhu Bi, Zhuofei Li, Liting Jiang, Yanhui Luo, Yuming Lin, Qing Fu, Zhiqiang Rufu, Chen J Cell Mol Med Original Articles Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non‐coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC. Linc00511 levels in PDAC tissue specimens and cell lines were examined by quantitative real‐time PCR. Corresponding adjacent non‐neoplastic tissues were used as controls. The function of linc00511 in PDAC cell lines was determined by RNA interference approach in vitro and in vivo. Fluorescence in situ hybridization (FISH) was used to characterize linc00511 expression in PDAC cells. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were obtained from bioinformatic analysis, luciferase assays and RIP assays. The association between the linc00511/hsa‐miR29b‐3p axis and VEGFA was verified by Western blotting assay. Immunohistochemistry was performed to evaluate the expression of VEGFA in PDAC samples. The aberrant up‐regulation of linc00511 was detected in PDAC cell lines and patient specimens compared with controls. An increase in linc00511 expression indicates the adverse clinical pathological characteristics and poor prognosis. Functionally, linc00511 depletion in PDAC cells decreased proliferation, migration, invasion and endothelial tube formation. Mechanistically, linc00511 could up‐regulate VEGFA via its competing endogenous RNA (ceRNA) activity on hsa‐miR‐29b‐3p. In summary, our results define an important axis controlling proliferation, invasion and tumour angiogenesis in PDAC. Linc00511 is a novel lncRNA that plays a significant regulatory role in the pathogenesis and progression of PDAC. Thus, Linc00511 represents a new prognostic biomarker to predict clinical outcome of PDAC patients after surgery and may serve as a potential therapeutic target for PDAC treatment. John Wiley and Sons Inc. 2017-10-05 2018-01 /pmc/articles/PMC5742682/ /pubmed/28984028 http://dx.doi.org/10.1111/jcmm.13351 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zhao, Xiaohui
Liu, Yimin
Li, Zhihua
Zheng, Shangyou
Wang, Zairui
Li, Wenzhu
Bi, Zhuofei
Li, Liting
Jiang, Yanhui
Luo, Yuming
Lin, Qing
Fu, Zhiqiang
Rufu, Chen
Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma
title Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma
title_full Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma
title_fullStr Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma
title_full_unstemmed Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma
title_short Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma
title_sort linc00511 acts as a competing endogenous rna to regulate vegfa expression through sponging hsa‐mir‐29b‐3p in pancreatic ductal adenocarcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742682/
https://www.ncbi.nlm.nih.gov/pubmed/28984028
http://dx.doi.org/10.1111/jcmm.13351
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