NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo

Abstract Background NEAT1 has been shown to play an oncogenic role in many kinds of cancers. However, detailed roles of NEAT1 in bladder cancer are largely unknown. Methods In the present study, the expression of NEAT1, miR-101 and VEGF-C was detected in human bladder cancer samples. The relationshi...

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Main Authors: Huihui Zhang, Shuang Yu, Kuilin Fei, Zhongxin Huang, Shidong Deng, Hanfeng Xu
Format: Article
Language:English
Published: BMC 2022-11-01
Series:BMC Urology
Subjects:
Online Access:https://doi.org/10.1186/s12894-022-01151-z
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author Huihui Zhang
Shuang Yu
Kuilin Fei
Zhongxin Huang
Shidong Deng
Hanfeng Xu
author_facet Huihui Zhang
Shuang Yu
Kuilin Fei
Zhongxin Huang
Shidong Deng
Hanfeng Xu
author_sort Huihui Zhang
collection DOAJ
description Abstract Background NEAT1 has been shown to play an oncogenic role in many kinds of cancers. However, detailed roles of NEAT1 in bladder cancer are largely unknown. Methods In the present study, the expression of NEAT1, miR-101 and VEGF-C was detected in human bladder cancer samples. The relationship between NEAT1 and the prognosis of patients with bladder cancer was analysed. In vitro experiments explored the effects of NEAT1 on biological behaviours of bladder cancer T24 and 5637 cells. Bioinformatics prediction and luciferase assays were used to assay the regulatory mechanism of action of NEAT1 and miR-101. Loss and gain of the expression of miR-101 and VEGF-C were used to explore the effects of the NEAT1/miR-101/VEGF-C pathway on T24 and 5637 cells. The effect of NEAT1 on the growth of bladder cancer in vivo was explored using an orthotopic tumourigenesis model. Results NEAT1 and VEGF-C were significantly upregulated in bladder cancer samples, and miR-101 was significantly downregulated. NEAT1 upregulation was associated with poorer recurrence-free survival of patients with bladder cancer. Overexpression of NEAT1 promoted the proliferation, migration and invasion of bladder cancer cells. The results of the luciferase assay indicated that miR-101 was a target of NEAT1. The promoting effects of NEAT1 on bladder cancer cells were reversed by miR-101 upregulation, and inhibition of miR-101 enhanced the effects of NEAT1. Overexpression of VEGF-C had a clear synergistic effect with the action of NEAT1. Overexpression of NEAT1 increased tumour growth and induced the development of liver metastasis. Conclusions In conclusion, our data indicated that NEAT1 was expressed at high levels in bladder cancer patients and correlated with unfavourable prognosis. NEAT1 promoted malignant development of bladder cancer in vitro and in vivo by regulating the miR-101/VEGF-C pathway.
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spelling doaj.art-78e5249d198e492cae3178586e3fff802022-12-22T03:44:03ZengBMCBMC Urology1471-24902022-11-0122111210.1186/s12894-022-01151-zNEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivoHuihui Zhang0Shuang Yu1Kuilin Fei2Zhongxin Huang3Shidong Deng4Hanfeng Xu5Department of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Urology, The People’s Hospital of LiuyangDepartment of Obstetrics, Xiangya Hospital, Central South UniversityDepartment of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaAbstract Background NEAT1 has been shown to play an oncogenic role in many kinds of cancers. However, detailed roles of NEAT1 in bladder cancer are largely unknown. Methods In the present study, the expression of NEAT1, miR-101 and VEGF-C was detected in human bladder cancer samples. The relationship between NEAT1 and the prognosis of patients with bladder cancer was analysed. In vitro experiments explored the effects of NEAT1 on biological behaviours of bladder cancer T24 and 5637 cells. Bioinformatics prediction and luciferase assays were used to assay the regulatory mechanism of action of NEAT1 and miR-101. Loss and gain of the expression of miR-101 and VEGF-C were used to explore the effects of the NEAT1/miR-101/VEGF-C pathway on T24 and 5637 cells. The effect of NEAT1 on the growth of bladder cancer in vivo was explored using an orthotopic tumourigenesis model. Results NEAT1 and VEGF-C were significantly upregulated in bladder cancer samples, and miR-101 was significantly downregulated. NEAT1 upregulation was associated with poorer recurrence-free survival of patients with bladder cancer. Overexpression of NEAT1 promoted the proliferation, migration and invasion of bladder cancer cells. The results of the luciferase assay indicated that miR-101 was a target of NEAT1. The promoting effects of NEAT1 on bladder cancer cells were reversed by miR-101 upregulation, and inhibition of miR-101 enhanced the effects of NEAT1. Overexpression of VEGF-C had a clear synergistic effect with the action of NEAT1. Overexpression of NEAT1 increased tumour growth and induced the development of liver metastasis. Conclusions In conclusion, our data indicated that NEAT1 was expressed at high levels in bladder cancer patients and correlated with unfavourable prognosis. NEAT1 promoted malignant development of bladder cancer in vitro and in vivo by regulating the miR-101/VEGF-C pathway.https://doi.org/10.1186/s12894-022-01151-zNEAT1miR-101VEGF-CBladder cancer
spellingShingle Huihui Zhang
Shuang Yu
Kuilin Fei
Zhongxin Huang
Shidong Deng
Hanfeng Xu
NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo
BMC Urology
NEAT1
miR-101
VEGF-C
Bladder cancer
title NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo
title_full NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo
title_fullStr NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo
title_full_unstemmed NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo
title_short NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo
title_sort neat1 promotes the malignant development of bladder cancer by regulating the mir 101 vegf c pathway in vitro and in vivo
topic NEAT1
miR-101
VEGF-C
Bladder cancer
url https://doi.org/10.1186/s12894-022-01151-z
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