Long non-coding RNA urothelial cancer associated 1 regulates radioresistance via the hexokinase 2/glycolytic pathway in cervical cancer

Abstract

Cervical cancer is one of the most common types of female malignant tumor. It is well established that radiotherapy (RT) is the first-line treatment of cervical cancer; however, radioresistance is a substantial obstacle to cervical cancer RT. At present, the mechanism underlying radioresistance remains unclear. Emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) function as crucial regulators of diverse cancers. Aerobic glycolysis, which is a common phenomenon in cancer cells, is associated with various biological functions, including radioresistance. To the best of our knowledge, the present study is the first to explore the role of the lncRNA urothelial cancer associated 1 (UcA1) in cervical cancer radioresistance. In the present study, irradiation was used to establish irradiation-resistant (IRR) cells, after which a clonogenic survival assay was used to validate radioresistance, reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression levels of UCA1 and western blotting was conducted to detect the expression levels of glycolysis-related proteins. In addition, a glucose/lactate assay kit was used to evaluate glucose/lactate concentrations and cells were transfected with small interfering RNA/pcdNA to regulate the expression of UCA1. Following the establishment of IRR cell lines (SiHa-IRR and HeLa-IRR), it was demonstrated that SiHa-IRR and HeLa-IRR cells exhibited increased expression levels of UCA1 and enhanced glycolysis. dysregulation of UcA1 and inhibition of glycolysis affected radioresistance of cervical cancer cells. In addition, the results indicated that UcA1 promoted radioresistance-associated glycolysis in SiHa-IRR and HeLa-IRR cells, with the enzyme hexokinase 2 (HK2) acting as a significant regulator in this process. Inhibiting glycolysis by 2-dG reversed the effects of UCA1 overexpression on HK2 protein expression and radioresistance in SiHa and HeLa cells. Taken together, these findings suggested that UcA1 may have an important role in regulating radioresistance through the HK2/glycolytic pathway, providing novel potential targets to improve cervical cancer RT.