长链非编码RNA LINC-PINT通过Hippo/YAP信号通路在缺氧诱导的头颈部鳞状细胞癌药物敏感性中的作用研究

doi:10.11904/j.issn.1002-3070.2023.06.002

实用肿瘤学杂志 ›› 2023, Vol. 37 ›› Issue (6): 466-471.doi: 10.11904/j.issn.1002-3070.2023.06.002

长链非编码RNA LINC-PINT通过Hippo/YAP信号通路在缺氧诱导的头颈部鳞状细胞癌药物敏感性中的作用研究

薛羽婷¹, 毛雄辉², 孙冀², 苑振楠²

1.齐齐哈尔医学院附属第三医院肿瘤内科(齐齐哈尔 161099);
2.哈尔滨医科大学附属肿瘤医院头颈外科

收稿日期:2022-10-26 修回日期:2023-06-12 出版日期:2023-12-28 发布日期:2024-03-18
通讯作者: 苑振楠,E-mail:yuanzhennan123@163.com
作者简介:薛羽婷,女,(1993-),硕士,住院医师,从事头颈部恶性肿瘤的研究。
基金资助:
哈尔滨医科大学附属肿瘤医院海燕基金课题(编号:JJZD2022-15)

The role of long-chain non-coding RNA LINC-PINT in drug sensitivity of hypoxia induced in head and neck squamous cell carcinoma through the Hippo/YAP signaling pathway

XUE Yuting¹, MAO Xionghui², SUN Ji², YUAN Zhennan²

1. Department of Oncology,the Third Affiliated Hospital of Qiqihar Medical University,Qiqihar 161099,China;
2. Department of Head and Neck Surgery,Harbin Medical University Cancer Hospital

Received:2022-10-26 Revised:2023-06-12 Online:2023-12-28 Published:2024-03-18

摘要/Abstract

摘要： 目的探讨长链非编码RNA LINC-PINT通过Hippo/Yes相关蛋白(YAP)信号通路在缺氧诱导的头颈部鳞状细胞癌(HNSCC)药物敏感性中的作用。方法 CCK-8法检测低氧环境中HNSCC细胞系(AGZY-973、HN4和HN30细胞)及正常人口腔角质形成细胞(NHOKs)增殖变化;取状态较好的HN30细胞,设置为正常组、低氧组、低氧+LINC-PINT过表达组、低氧+过表达阴性对照组。qRT-PCR检测HN30细胞中LINC-PINT表达水平;CCK-8法检测HN30细胞的药物敏感性及顺铂对HN30细胞增殖影响;流式细胞术检测细胞凋亡;Western blot检测HN30细胞缺氧诱导因子1α(HIF-1α)、p-YAP、YAP蛋白表达水平。结果在低氧条件下,AGZY-973细胞、HN4细胞和HN30细胞增殖率较NHOKs细胞显著增加(P＜0.05)。与正常组相比,低氧组HN30细胞IC₅₀值、HIF-1α、p-YAP/YAP表达显著增加,细胞凋亡率、24 h和48 h细胞生长抑制率、LINC-PINT表达水平显著降低(P＜0.05);与低氧+过表达阴性对照组相比,低氧+LINC-PINT过表达组HN30细胞IC₅₀值、HIF-1α、p-YAP/YAP表达显著降低,细胞凋亡率、24 h和48 h细胞生长抑制率、LINC-PINT表达水平显著增加(P＜0.05)。结论过表达LINC-PINT可提高缺氧诱导的HNSCC顺铂敏感性,可能与抑制Hippo/YAP信号通路的激活有关。

关键词: 长链非编码RNA LINC-PINT, 头颈部鳞状细胞癌, 缺氧, 药物敏感性, Hippo/YAP信号通路

Abstract: Objective The aim of this study was to investigate the role of long chain non-coding RNA LINC-PINT in drug sensitivity of hypoxia induced in head and neck squamous cell carcinoma(HNSCC)through the Hippo/Yes-associated protein(YAP)signaling pathway. Methods The proliferative changes of HNSCC cell lines(AGZY-973 cells,HN4 cells,and HN30 cells)and normal human oral keratinocytes(NHOKs)in hypoxic environment were detected by CCK-8 assay;HN30 cells in good condition were taken and set them as the normal group,hypoxia group,hypoxia+LINC-PINT overexpression group,and hypoxia+overexpression negative control group.The expression of LINC-PINT in HN30 cells was detected by qRT-PCR;CCK-8 assay was applied to detect the drug sensitivity of HN30 cells,and the effect of cisplatin on proliferation in HN30 cells;cell apoptosis was detected by flow cytometry;and Western blot was applied to detect the expression of hypoxia inducible factor-1α(HIF-1α),p-YAP,and YAP protein in HN30 cells. Results Under hypoxia conditions,the proliferative rates of AGZY-973 cells,HN4 cells and HN30 cells were obviously higher than that of NHOKs cells(P＜0.05).Compared with the normal group,the IC₅₀ value,the expression of HIF-1α and p-YAP/YAP in the hypoxic group were obviously increased in HN30 cells,the rate of apoptosis,the rates of cell growth inhibition at 24 h and 48 h,and the expression of LINC-PINT protein were obviously decreased(P＜0.05);Compared with the hypoxia+overexpression negative control group,the IC₅₀ values,the expression of HIF-1α and p-YAP/YAP cells in the hypoxia overexpression of LINC-PINT group was obviously reduced in HN30,the rates of apoptosis,the rates of cell growth inhibition at 24 h and 48 h,and the expression of LINC-PINT protein were significantly increased(P＜0.05). Conclusion Overexpression of LINC-PINT can enhance the hypoxia-induced cisplatin sensitivity in HNSCC,which may be related to the inhibition of the activation of Hippo/YAP signaling pathway.

Key words: Long chain non-coding RNA LINC-PINT, Head and neck squamous cell carcinoma, Hypoxia, Drug sensitivity, Hippo/YAP signaling pathway

中图分类号:

R739

薛羽婷, 毛雄辉, 孙冀, 苑振楠. 长链非编码RNA LINC-PINT通过Hippo/YAP信号通路在缺氧诱导的头颈部鳞状细胞癌药物敏感性中的作用研究[J]. 实用肿瘤学杂志, 2023, 37(6): 466-471.

XUE Yuting, MAO Xionghui, SUN Ji, YUAN Zhennan. The role of long-chain non-coding RNA LINC-PINT in drug sensitivity of hypoxia induced in head and neck squamous cell carcinoma through the Hippo/YAP signaling pathway[J]. Journal of Practical Oncology, 2023, 37(6): 466-471.

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http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2023/V37/I6/466

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长链非编码RNA LINC-PINT通过Hippo/YAP信号通路在缺氧诱导的头颈部鳞状细胞癌药物敏感性中的作用研究

The role of long-chain non-coding RNA LINC-PINT in drug sensitivity of hypoxia induced in head and neck squamous cell carcinoma through the Hippo/YAP signaling pathway

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