Cisplatin-based
chemotherapy and
radiotherapy are the main first-line treatment strategies for
nasopharyngeal carcinoma (NPC) patients. Unfortunately, resistance is a major obstacle in the clinical management of NPC patients. We prove that the expression level of high-mobility group box 1 (
HMGB1) is dramatically increased in resistant NPC cells than that in sensitive cells.
HMGB1 induces the expression and secretion of
IL6, which leads to constitutive autocrine activation of the JAK2/STAT3 pathway and eventually contributes to chemoresistance in NPC cells. Long non-coding RNAs (lncRNAs) have been identified as key regulators involved in drug resistance. In this study, using GO analysis of the biological process and differential expression analysis, we find 12 significantly altered IncRNAs in NPC cell lines, which may be involved in regulating gene expression. Furthermore, we determine that elevated
lncRNA MIAT level upregulates
HMGB1 expression, contributing to
cisplatin resistance in NPC cells. We find that the deficiency of the
lncRNA MIAT/
HMGB1 axis, inhibition of JAK2/STAT3, or neutralization of
IL6 by
antibodies significantly re-sensitizes resistant NPC cells to
cisplatin in resistant NPC cells. Moreover, we provide the in vivo evidence that the deficiency of
HMGB1 reduces
cisplatin-resistant
tumor growth. Most importantly, we provide clinical evidence showing that the expression level of the
lncRNA MIAT/
HMGB1/
IL6 axis is elevated in resistant NPC
tumors, which is highly correlated with poor clinical outcome. Our findings identify a novel chemoresistance mechanism regulated by the
lncRNA MIAT/
HMGB1/
IL6 axis, which indicates the possibilities for
lncRNA MIAT,
HMGB1, and
IL6 as
biomarkers for chemoresistance and targets for developing novel strategies to overcome resistance in NPC patients.