<scp>lncRNA PVT1</scp> promotes cetuximab resistance of head and neck squamous cell carcinoma cells by inhibiting <scp>miR</scp>‐124‐3p
Shuo Yang, Zhijun Yuan, Yue‐Hong Zhu, Chen Xue, Wei Wang
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.