Long non-coding RNA urothelial cancer associated 1 regulates radioresistance via the hexokinase 2/glycolytic pathway in cervical cancer
Long non-coding RNA urothelial cancer associated 1 regulates radioresistance via the hexokinase 2/glycolytic pathway in cervical cancer
复制标题
DOI：
10.3892/ijmm.2018.3778
复制
发表时间：
2018-10-01
影响因子：
5.4
通讯作者：
Yao, Tingting
中科院分区：
文献类型：
--
作者：
Fan, Li;Huang, Chunxian;Yao, Tingting
宫颈癌是女性最常见的恶性肿瘤之一。众所周知，放射治疗 (RT) 是宫颈癌的一线治疗方法；然而，放射抗性是宫颈癌放疗的一个重大障碍。目前，辐射抗性的机制尚不清楚。新的证据表明，长链非编码 RNA (lncRNA) 是多种癌症的关键调节因子。有氧糖酵解是癌细胞中的常见现象，与多种生物功能相关，包括抗辐射性。据我们所知，本研究首次探讨了lncRNA尿路上皮癌相关1（UCA1）在宫颈癌放射抵抗中的作用。在本研究中，利用辐射建立抗辐射（IRR）细胞，然后使用克隆存活实验验证辐射抗性，使用逆转录定量聚合酶链反应评估UCA1的表达水平，并进行蛋白质印迹检测糖酵解相关蛋白的表达水平。此外，使用葡萄糖/乳酸测定试剂盒评估葡萄糖/乳酸浓度，并用小干扰RNA/pcDNA转染细胞以调节UCA1的表达。建立 IRR 细胞系（SiHa-IRR 和 HeLa-IRR）后，证明 SiHa-IRR 和 HeLa-IRR 细胞表现出 UCA1 表达水平增加和糖酵解增强。 UCA1 失调和糖酵解抑制影响宫颈癌细胞的放射抗性。此外，结果表明，UCAI 促进了 SiHa-IRR 和 HeLa-IRR 细胞中与放射抗性相关的糖酵解，己糖激酶 2 (HK2) 在此过程中起着重要的调节作用。通过 2-DG 抑制糖酵解可逆转 UCAI 过表达对 SiHa 和 HeLa 细胞中 HK2 蛋白表达和放射抗性的影响。总而言之，这些发现表明 UCA1 可能在通过 HK2/糖酵解途径调节放射抗性中发挥重要作用，为改善宫颈癌 RT 提供新的潜在靶点。
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 UCAI 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 UCAI 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.