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miR-137/ERRα axis mediates chemoresistance of nasopharyngeal carcinoma cells
Journal of Cell Communication and Signaling ( IF 4.1 ) Pub Date : 2021-07-01 , DOI: 10.1007/s12079-021-00634-2
Fei Liu 1 , Chunsheng Gao 1 , Wenjuan Wang 2 , Jing Hu 1 , Zuofeng Huang 1 , Meng Liang 1 , Shuo Li 1
Affiliation  

Nasopharyngeal carcinoma (NPC) is the most common malignant tumor of the head and neck region and is characterized by an increased risk of developing chemoresistance after treatment. The present study demonstrated that estrogen-related receptor α (ERRα) was upregulated in cisplatin- and fluorouracil-resistant NPC cells. In addition, ERRα knockdown or treatment of cells with the ERRα inverse agonist XCT-790 attenuated the chemoresistance of NPC cells. Mechanistically, the increased expression of ERRα in chemoresistant cells was associated with enhanced mRNA stability. Bioinformatics analysis for screening microRNAs (miRs) regulating the expression of ERRα revealed that miR-137 was downregulated in chemoresistant NPC cells. Additionally, transfection of cells with miR-137 mimics reduced ERRα mRNA stability and increased the chemosensitivity of NPC cells. Furthermore, ERRα knockdown reduced glucose consumption, and lactate and ATP production rates in chemoresistant cells. The aforementioned findings suggested that the miR-137/ERRα-mediated metabolic programming could be involved in the chemoresistance of NPC cells.



中文翻译:

miR-137/ERRα轴介导鼻咽癌细胞的化学抗性

鼻咽癌 (NPC) 是头颈部最常见的恶性肿瘤,其特点是治疗后发生化疗耐药的风险增加。本研究表明,雌激素相关受体 α (ERRα) 在顺铂和氟尿嘧啶耐药的 NPC 细胞中上调。此外,ERRα 敲低或用 ERRα 反向激动剂 XCT-790 处理细胞减弱了 NPC 细胞的化学抗性。从机制上讲,化学抗性细胞中ERRα的表达增加与mRNA稳定性增强有关。筛选调节 ERRα 表达的 microRNA (miR) 的生物信息学分析显示,miR-137 在化学抗性 NPC 细胞中下调。此外,用 miR-137 模拟物转染细胞会降低 ERRα mRNA 的稳定性并增加 NPC 细胞的化学敏感性。此外,ERRα 敲低降低了化学抗性细胞中的葡萄糖消耗,以及乳酸和 ATP 的产生率。上述发现表明 miR-137/ERRα 介导的代谢程序可能与 NPC 细胞的化学抗性有关。

更新日期:2021-07-01
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