lncRNA HOTAIR regulates radio-resistance in squamous cell carcinoma of the tongue by Notch signaling.

OBJECTIVE

To minimize local recurrence of tongue cancer, it is necessary to tackle the issues of radiotherapy resistance and sensitivity in tongue squamous cell carcinoma (TSCCa). This study focuses on understanding how HOX transcript antisense intergenic RNA (HOTAIR) influences resistance to radiotherapy in TSCCa by modulating the Notch signaling pathway.

METHODS

The TSCCa cells SCC9 and SCC25 were divided into six experimental groups: (1) 8 Gy irradiation group, (2) 8 Gy with negative control, (3) 8 Gy with silent HOTAIR, (4) 8 Gy with null control, (5) 8 Gy with overexpressing HOTAIR, and (6) 8 Gy with silent HOTAIR and Jagged1. After assessing changes in apoptosis, proliferation, and invasion abilities of cells in each group using CCK-8, flow cytometry, and Transwell assays, we also utilized qRT-PCR and WesternBlot to evaluate changes in genes and proteins associated with the Notch pathway. These alterations induced by HOTAIR were validated in vivo using nude mouse tumor-bearing model.

RESULTS

In the silenced HOTAIR group, both ex vivo and in vivo studies revealed decreased cell survival and invasiveness, increased apoptosis, and significantly reduced expression of Notch1, Jagged1, and HES-1 at gene and protein levels (all P < 0.05). In contrast, adding an agonist of the Notch signaling pathway produced opposite results (all P < 0.05).

CONCLUSION

The regulation of the Notch signaling pathway by HOTAIR is associated with resistance to radiotherapy in squamous cell carcinoma of the tongue.