A microRNA-27a mimic sensitizes human oral squamous cell carcinoma HSC-4 cells to hyperthermia through downregulation of Hsp110 and Hsp90.

Abstract

Hyperthermia (HT) is an important modality in cancer treatment; however, the acquisition of thermal resistance in cancer cells due to the elevation of heat shock proteins (HSPs) makes HT less effective. Accumulating evidence suggests that microRNAs (miRNAs) play an important role in regulating cellular stress sensitivities, such as drug sensitivity and radio-sensitivity, in cancer cells. However, few studies have investigated the involvement of miRNAs in thermal sensitivity. The aim of this study was thus to investigate the contribution of miRNAs to the thermal sensitivity of human oral squamous cell carcinoma (OSCC) cells. When the HSC-2, HSC-3 and HSC-4 OSCC cell lines were treated with HT at 44˚C for 60 min, a significant increase in cell death was observed in HSC-2 and HSC-3 cells but not HSC-4 cells, suggesting that HSC-4 cells were thermally resistant under the present experimental conditions. Moreover, the expression levels of HSPs were most elevated in HSC-4 cells. When the basal expression levels of miRNAs were monitored using two different microarray systems in thermal-sensitive HSC-2 and HSC-3 cells and thermal-resistant HSC-4 cells, five miRNAs that were differentially expressed were identified. Among these miRNAs, the expression level of miR-27a in HSC-4 cells was markedly reducec compared to the expression levels in HSC-2 and HSC-3 cells. Interestingly, treatment of HSC-4 cells with a miR-27a mimic oligonucleotide significantly enhanced HT-induced cell death. Furthermore, the miR-27a mimic oligonucleotide suppressed the elevation of the expression of Hsp90 and Hsp110 in HSC-4 cells, suggesting that these HSPs may be involved in a mechanism of thermal resistance. From these findings, we concluded that in OSCC cells, miR-27a may contribute to thermal sensitivity by modulating the HSP expression.