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,Zhi-Jun Yuan,Yue-Hong Zhu,Xue Chen,Wei Wang
出处
期刊:Head & neck
[Wiley]
日期:2021-05-25
卷期号:43 (9): 2712-2723
被引量:3
摘要
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.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).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.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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