长链非编码RNA TUG1对鼻咽癌细胞生物学行为及放射敏感性的影响

Effect of LncRNA TUG1 on biological behavior and radiosensitivity of nasopharyngeal carcinoma

目的对长链非编码RNA TUG1进行泛癌分析,并评估其对鼻咽癌生物学行为及放射敏感性的影响。方法基于TCGA数据库检测TUG1在泛癌中的表达情况和预后价值。用qPCR方法检测鼻咽癌组织和鼻咽癌细胞系中TUG1的表达情况。用TUG1 siRNA或阴性对照siRNA转染鼻咽癌CNE-1和CNE-2细胞。采用MTS法、transwell实验和划痕实验检测鼻咽癌细胞的增殖、侵袭和迁移能力。细胞克隆形成实验测定细胞放射敏感性。流式细胞仪检测细胞周期和凋亡情况。结果基于TCGA数据库的分析发现,在12种癌症类型中TUG1的表达上调。TUG1表达增加与多种癌症类型的较差预后相关。体外实验研究发现lncRNA TUG1在鼻咽癌细胞系和组织中也显著上调。TUG1高表达与TNM分期恶化有显著相关性。TUG1的高表达与鼻咽癌患者不良预后有显著相关性。下调TUG1的表达可抑制鼻咽癌细胞的增殖、迁移和侵袭,促进鼻咽癌细胞凋亡,提高鼻咽癌细胞放射敏感性。结论TUG1在多种癌症类型中发挥重要作用,并与鼻咽癌的不良预后相关。TUG1可能作为鼻咽癌治疗的潜在治疗靶点。

Objective Radiotherapy is the standard treatment for nasopharyngeal carcinoma(NPC).Increasing evidence shows that long non-coding RNA(lncRNAs)plays an important role in regulating cell radiosensitivity.However,the role of TUG1 in radiation resistance of NPC has not been studied.This study is to perform pan-cancer analysis of TUG1,and to evaluate its effect on biological behavior and radiosensitivity of NPC.Methods Expression and prognostic value of TUG1 in pan-cancer were detected based on TCGA database.qPCR was used to detect the expression of TUG1 in NPC tissues and NPC cell lines.CNE-1 and CNE-2 cells were transfected with TUG1 siRNA or negative control siRNA.The proliferation,invasion and migration of NPC cells were detected by MTS,transwell and scratch test.The radiosensitivity of cells was measured by cell clone formation.The cell cycle and apoptosis were detected by flow cytometry.Results Analysis based on TCGA database showed that the expression of TUG1 was up-regulated in 12 cancer types.The increased expression of TUG1 was associated with poor prognosis in many types of cancers.In vitro studies showed that TUG1 was also significantly up-regulated in NPC cell lines and tissues.There was a significant association between TUG1 overexpression and worse TNM stage.Moreover,high expressionof TUG1 in NPC was determined to be a strongpredictor of short overall survival.Further investigation found that knockdown of TUG1 repressed proliferation,migration and invasion,promoted apoptosis,and improved radiosensitivity.Conclusion Our results reveal the important role of TUG1 in many types of cancers and it is related to the poor prognosis of NPC.TUG1may serve as novel targets for NPC therapy.