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。
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 IC 50 value,the expression of HIF-1αand 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 IC 50 values,the expression of HIF-1αand 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.
作者
薛羽婷
毛雄辉
孙冀
苑振楠
XUE Yuting;MAO Xionghui;SUN Ji;YUAN Zhennan(Department of Oncology,the Third Affiliated Hospital of Qiqihar Medical University,Qiqihar 161099,China;Department of Head and Neck Surgery,Harbin Medical University Cancer Hospital)
出处
《实用肿瘤学杂志》
CAS
2023年第6期466-471,共6页
Practical Oncology Journal
基金
哈尔滨医科大学附属肿瘤医院海燕基金课题(编号:JJZD2022-15)。
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;通信作者:苑振楠,E-mail:yuanzhennan123@163.com。
