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circPGAM1 enhances autophagy signaling during laryngocarcinoma drug resistance by regulating miR-376a
Biochemical and Biophysical Research Communications ( IF 3.1 ) Pub Date : 2020-10-26 , DOI: 10.1016/j.bbrc.2020.10.063
Bo Feng 1 , Ke Chen 2 , Weiwei Zhang 1 , Qi Zheng 1 , Yong He 1
Affiliation  

circRNAs have been shown to be involved in cancer progression. It is unclear whether circPGAM1 exerts its effect on laryngocarcinoma drug resistance. In this study, we employed colony formation and MTT assay to determine colony number and cell viability under cisplatin treatment. TUNEL experiment was used to evaluate apoptosis of laryngocarcinoma cells in the presence of cisplatin. Xenograft tumor experiment was performed to assess in vivo tumor growth of SNU46 cells. We found that circPGAM1 enhanced colony formation and viability of SNU46 and M4E cells. In contrast, circPGAM1 caused attenuated cell apoptosis. Furthermore, we also confirmed that circPGAM1 played a key role in tumor growth in animal model and clinical patients. miR-376a was identified and proved to act as key effector for circPGAM1-mediated drug resistance. Finally, autophagy-related gene ATG2A was shown to rescue miR-376a-modulated drug resistance of laryngocarcinoma cells. Herein, we illuminate the role of circPGAM1 in laryngocarcinoma drug resistance, thereby facilitating development of targeted therapy for treating laryngocarcinoma.



中文翻译:

circPGAM1通过调节miR-376a增强喉癌耐药过程中的自噬信号转导

已证明circRNA与癌症进展有关。尚不清楚circPGAM1是否对喉癌的耐药性发挥作用。在这项研究中,我们采用集落形成和MTT分析来确定顺铂处理后的集落数和细胞活力。TUNEL实验用于评价顺铂存在下喉癌细胞的凋亡。进行异种移植肿瘤实验以评估SNU46细胞的体内肿瘤生长。我们发现circPGAM1增强了SNU46和M4E细胞的集落形成和活力。相反,circPGAM1导致细胞凋亡减少。此外,我们还证实circPGAM1在动物模型和临床患者的肿瘤生长中起着关键作用。miR-376a被鉴定并证明是circPGAM1介导的耐药性的关键效应子。最后,自噬相关基因ATG2A被证明可以挽救miR-376a调节的喉癌细胞耐药性。在此,我们阐明了circPGAM1在喉癌耐药中的作用,从而促进了靶向治疗喉癌的发展。

更新日期:2020-10-30
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