Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression

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.

High‐mobility group box 1 protein modulated proliferation and radioresistance in esophageal squamous cell carcinoma

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Long non-coding RNA TUG1 recruits miR‑29c‑3p from its target gene RGS1 to promote proliferation and metastasis of melanoma cells

“…TUG1 is a critical regulator of cell proliferation in several cancer types, such as glioblastoma (35), osteosarcoma (26), bladder cancer (36) and colorectal cancer (37). TUG1 participates in the proliferation, migration, invasion and apoptosis of cancer cells.…”

Radiosensitization of esophageal carcinoma cells by knockdown of HMGB1 expression

“…Therefore, the discovery of effective therapeutic targets to enhance radiosensitivity may improve the survival of ESCC patients. The overexpression of HMGB1 has been implicated in multiple cancers, including breast (18), rectal (11), bladder (19) and gallbladder cancer (20), pleural mesothelioma (21), nasopharyngeal carcinoma (22), and esophageal cancer (23). During tumor development and cancer treatment, diverse roles for HMGB1 have been revealed in previous studies, including roles in inflammation (24), immune responses (25), angiogenesis (26), DNA damage repair (27), autophagy (28), proliferation, apoptosis, invasion and metastasis (29,30).…”