Mao Minghuan, Yang Liang, Hu Jingyao, Liu Bing, Liu Chunlai, Zhang Xiling, Liu Yili, Wang Ping, Li Hangyu
Department of Urology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110000, PR China.
Department of General Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110000, PR China.
Genomics. 2021 Jul;113(4):2122-2133. doi: 10.1016/j.ygeno.2021.04.033. Epub 2021 Apr 22.
This study aimed to investigate the function of OCT3/4 on tumor immune escape in bladder cancer. Initially, the expression of OCT3/4, TET1, NRF2 and MDM2 was quantified in tumor tissues and cells, followed by gain- or loss-of-function studies to define their roles in cell migration, invasion and apoptosis and tumorigenicity in nude mice. Bladder cancer presented with abundant expression levels of OCT3/4, TET1, NRF2 and MDM2. We found that OCT3/4 promoted TET1 expression via binding to its promoter and that TET1 recruited MLL protein to NRF2 promoter and upregulated its expression, while NRF2 enhanced MDM2 expression. Upregulated MDM2 accelerated tumor immune escape in bladder cancer in mice. OCT3/4 knockdown suppressed the cell migration and invasion while inducing apoptosis, and consequently prevented tumor growth and immune escape in mice. Collectively, OCT3/4 may promote the progression of tumor immune escape in bladder cancer through acting as a promoter of the TET1/NRF2/MDM2 axis.
本研究旨在探讨OCT3/4在膀胱癌肿瘤免疫逃逸中的作用。首先，对肿瘤组织和细胞中OCT3/4、TET1、NRF2和MDM2的表达进行定量，随后进行功能获得或缺失研究，以确定它们在细胞迁移、侵袭、凋亡以及裸鼠致瘤性中的作用。膀胱癌呈现出OCT3/4、TET1、NRF2和MDM2的高表达水平。我们发现，OCT3/4通过与TET1启动子结合促进其表达，而TET1将MLL蛋白募集到NRF2启动子并上调其表达，同时NRF2增强MDM2的表达。上调的MDM2加速了小鼠膀胱癌的肿瘤免疫逃逸。敲低OCT3/4可抑制细胞迁移和侵袭，同时诱导凋亡，从而抑制小鼠肿瘤生长和免疫逃逸。总体而言，OCT3/4可能通过作为TET1/NRF2/MDM2轴的促进因子来推动膀胱癌肿瘤免疫逃逸的进展。
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