西妥昔单抗
PVT1型
头颈部鳞状细胞癌
癌症研究
甲基化
流式细胞术
下调和上调
DNA甲基化
细胞
长非编码RNA
化学
生物
分子生物学
癌症
基因表达
头颈部癌
抗体
免疫学
基因
单克隆抗体
生物化学
遗传学
作者
Shuo Yang,Zhijun Yuan,Yue‐Hong Zhu,Chen Xue,Wei Wang
出处
期刊:Head & neck
[Wiley]
日期:2021-05-25
卷期号:43 (9): 2712-2723
被引量:15
摘要
Abstract Background Cetuximab has been widely used in the clinical treatment of head and neck squamous cell carcinoma (HNSCC). However, whether long non‐coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) is correlated with cetuximab resistance remains unclear. Methods Western blot and qRT‐PCR were performed to quantify the levels of genes and proteins, respectively. Cell functions were measured using Cell Counting Kit‐8 (CCK‐8), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry assays. The methylation level was tested using methylation‐specific PCR (MSP). Results PVT1 was upregulated and positively correlated with the poor prognosis of HNSCC. PVT1 overexpression markedly promoted the survival and weakened the cetuximab sensitivity of HNSCC cells, while miR‐124‐3p overexpression showed opposite effects. Mechanistically, the silence of PVT1 indirectly promoted miR‐124‐3p expression by reducing its promoter methylation. Importantly, miR‐124‐3p overexpression impeded the regulatory roles of PVT1 overexpression. Conclusion PVT1 decreased the sensitivity of HNSCC cells to cetuximab by enhancing methylation‐mediated inhibition of miR‐124‐3p, which might provide a new insight for the cetuximab chemoresistance of HNSCC.
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