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circRNA-002178 act as a ceRNA to promote PDL1/PD1 expression in lung adenocarcinoma.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-01-16 , DOI: 10.1038/s41419-020-2230-9
JunFeng Wang 1 , XuHai Zhao 1 , YanBo Wang 1 , FengHai Ren 1 , DaWei Sun 1 , YuBo Yan 1 , XiangLong Kong 1 , JianLong Bu 1 , MengFeng Liu 1 , ShiDong Xu 1
Affiliation  

Circular RNAs (circRNAs) have been identified play a vital role in various different types of cancer via sponging miRNAs (microRNAs). However, their role in lung adenocarcinoma (LUAD) remains largely unclear. In this study, we systematically characterized the circRNA expression profiles in the LUAD cancer tissues and paired adjacent non-cancerous tissues. Three circRNAs were found to be significantly upregulated. Among them, has-circRNA-002178 was further confirmed to be upregulated in the LUAD tissues, and LUAD cancer cells. Subsequently, we also found has-circRNA-002178 could enhance PDL1 expression via sponging miR-34 in cancer cells to induce T-cell exhaustion. More importantly, circRNA-002178 could be detected in exosomes of plasma from LUAD patients and could serve as biomarkers for LUAD early diagnosis. Finally, we found circRNA-002178 could be delivered into CD8+ T cells to induce PD1 expression via exosomes. Taken together, our study revealed that circRNA-002178 could act as a ceRNA to promote PDL1/PD1 expression in lung adenocarcinoma.

中文翻译:

circRNA-002178作为ceRNA来促进肺腺癌中PDL1 / PD1的表达。

通过海绵状miRNA(microRNA),已鉴定出环状RNA(circRNA)在各种不同类型的癌症中起着至关重要的作用。但是,它们在肺腺癌(LUAD)中的作用仍不清楚。在这项研究中,我们系统地表征了LUAD癌组织和成对的相邻非癌组织中的circRNA表达谱。发现三个circRNA被显着上调。其中,has-circRNA-002178被进一步证实在LUAD组织和LUAD癌细胞中被上调。随后,我们还发现has-circRNA-002178可以通过在癌细胞中掺入miR-34来增强PDL1表达,从而诱导T细胞衰竭。更重要的是,可以在LUAD患者的血浆外泌体中检测到circRNA-002178,并可以作为LUAD早期诊断的生物标记。最后,我们发现circRNA-002178可通过外泌体传递到CD8 + T细胞中诱导PD1表达。两者合计,我们的研究表明,circRNA-002178可以作为ceRNA来促进肺腺癌中PDL1 / PD1的表达。
更新日期:2020-01-17
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