Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expressionReportar como inadecuado




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Radiation Oncology

, 12:65

First Online: 04 April 2017Received: 07 December 2016Accepted: 26 March 2017DOI: 10.1186-s13014-017-0802-3

Cite this article as: Jiang, H., Hu, X., Zhang, H. et al. Radiat Oncol 2017 12: 65. doi:10.1186-s13014-017-0802-3

Abstract

BackgroundLong non-coding RNAs lncRNAs have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 TUG1 has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear.

MethodsQuantitative real-time PCR qRT-PCR was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder cancer tissues and cell lines. HMGB1 protein levels were tested by western blot assays. Different doses of X-ray were used for radiation treatment of bladder cancer cells. Colony survival and cell viability were detected by clonogenic assay and CCK-8 Kit, respectively. Cell apoptosis was determined by flow cytometry. A xenograft mouse model was constructed to observe the effect of TUG1 on tumor growth in vivo.

ResultsThe levels of TUG1 and HMGB1 were remarkably increased in bladder cancer tissues and cell lines. Radiation treatment markedly elevated the expression of TUG1 and HMGB1. TUG1 knockdown inhibited cell proliferation, promoted cell apoptosis and decreased colony survival in SW780 and BIU87 cells under radiation. Moreover, TUG1 depletion suppressed the HMGB1 mRNA and protein levels. Furthermore, overexpression of HMGB1 reversed TUG1 knockdown-induced effect in bladder cancer cells. Radiation treatment dramatically reduced the tumor volume and weight in xenograft model, and this effect was more obvious when combined with TUG1 silencing.

ConclusionLncRNA TUG1 knockdown enhances radiosensitivity of bladder cancer by suppressing HMGB1 expression. TUG1 acts as a potential regulator of radioresistance of bladder cancer, and it may represent a promising therapeutic target for bladder cancer patients.

KeywordslncRNA TUG1 HMGB1 Bladder cancer Radiosensitivity AbbreviationsCRCColorectal cancer

EMTEpithelial-to-mesenchymal transition

HMGB1High mobility group box 1 protein

LncRNAsLong non-coding RNAs

MIBCMuscle invasive bladder cancer

NMIBCNon-muscle invasive bladder cancer

PDACPancreatic ductal adenocarcinoma

qRT-PCRquantitative real-time PCR

TUG1Taurine-upregulated gene 1

TUG1Taurine-upregulated gene 1

WIF-1Wnt inhibitory factor 1

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Autor: Huijuan Jiang - Xigang Hu - Hongzhi Zhang - Wenbo Li

Fuente: https://link.springer.com/







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