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TUSC8通过调节VEGFA增强非小细胞肺癌细胞对顺铂的敏感性。

TUSC8 enhances cisplatin sensitivity of NSCLC cells through regulating VEGFA.

作者信息

Shi Naiming, Feng Dengmei, Gu Yun, Zheng Chengyuan, Miao Miao

机构信息

Department of Thoracic Surgery, Lianshui People's Hospital, Huai'an, China.

出版信息

J BUON. 2021 Mar-Apr;26(2):336-344.

Abstract

PURPOSE

We aimed at studying LncRNA TUSC8 expression in non-small cell lung cancer (NSCLC) cells and its sensitivity to cisplatin chemotherapy, and explore its role in the occurrence, development and treatment of NSCLC.

METHODS

NSCLC tissues and adjacent normal ones were randomly selected from 45 patients in our hospital who were pathologically diagnosed as NSCLC. Then H358 and H1299 cells were treated with cisplatin at different concentrations (0 μM, 2 μM, 4 μM, 8 μM, 16 μM) for 24 hours.

RESULTS

Our data showed that long non-coding RNA (LncRNA) TUSC8 mRNA expression in NSCLC tissue specimens was remarkably lower than that in adjacent ones. A great link was found between LncRNA TUSC8 and tumor size, TNM stage and overall survival rates of patients with Lung cancer (LCa). The proliferation of NSCLC cells remarkably reduced after overexpression of LncRNA TUSC8 compared with the control group pcDNA3.1-NC, while cell apoptosis indicated an opposite trend. A binding relationship between LncRNA TUSC8 and its downstream target gene VEGFA was verified by luciferase assay. The proliferation rate of NSCLC cells decreased with the increase of cisplatin concentration, and the inhibition rate of LncRNA TUSC8 overexpression group was higher than that of the control group pcDNA3.1-NC under different concentrations of cisplatin.

CONCLUSIONS

Lowly expressed LncRNA TUSC8 in NSCLC is related to pathological parameters and prognosis of NSCLC patients. It may negatively regulate VEGFA by targeting its 3'UTR, thereby increasing the sensitivity of NSCLC cell lines to cisplatin, inhibiting the proliferation of NSCLC cells and promoting their apoptosis.

摘要

目的

本研究旨在探讨长链非编码RNA(LncRNA)TUSC8在非小细胞肺癌(NSCLC)细胞中的表达及其对顺铂化疗的敏感性,并探究其在NSCLC发生、发展及治疗中的作用。

方法

随机选取我院45例经病理诊断为NSCLC的患者的癌组织及癌旁正常组织。然后将H358和H1299细胞用不同浓度(0 μM、2 μM、4 μM、8 μM、16 μM)的顺铂处理24小时。

结果

我们的数据显示,NSCLC组织标本中长链非编码RNA(LncRNA)TUSC8 mRNA表达明显低于癌旁组织。发现LncRNA TUSC8与肺癌(LCa)患者的肿瘤大小、TNM分期及总生存率之间存在密切关联。与对照组pcDNA3.1-NC相比,LncRNA TUSC8过表达后NSCLC细胞的增殖明显降低,而细胞凋亡呈现相反趋势。荧光素酶报告基因实验验证了LncRNA TUSC8与其下游靶基因VEGFA之间的结合关系。NSCLC细胞的增殖率随顺铂浓度的增加而降低,在不同浓度顺铂作用下,LncRNA TUSC8过表达组的抑制率高于对照组pcDNA3.1-NC。

结论

NSCLC中低表达的LncRNA TUSC8与NSCLC患者的病理参数及预后相关。它可能通过靶向VEGFA的3'UTR对其进行负调控,从而增加NSCLC细胞系对顺铂的敏感性,抑制NSCLC细胞的增殖并促进其凋亡。

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