PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity.
PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity.
复制标题
PD-L1 lncRNA剪接亚型通过增强c-Myc活性促进肺腺癌进展
DOI：
10.1186/s13059-021-02331-0
复制
发表时间：
2021-04-13
期刊：
影响因子：
12.3
通讯作者：
Zen K
中科院分区：
文献类型：
--
作者：
Qu S;Jiao Z;Lu G;Yao B;Wang T;Rong W;Xu J;Fan T;Sun X;Yang R;Wang J;Yao Y;Xu G;Yan X;Wang T;Liang H;Zen K
尽管使用程序性死亡配体1(PD-L1)的阻断来增强T细胞免疫应答在肿瘤免疫治疗中显示出巨大的前景，但免疫检查点抑制策略在实体瘤患者中的应用有限。结果运用qRT-PCR、Sanger测序和RNA BaseScope分析，我们发现人类肺腺癌(LUAD)都通过选择性剪接产生PD-L1的长非编码RNA异构体(PD-L1-LNC)，无论肿瘤的PD-L1蛋白是阳性还是阴性。与PD-L1mRNA类似，干扰素γ可显著上调多种肺腺癌细胞中PD-L1-Lnc的表达。体外和体内研究表明，PD-L1-lnc促进肺腺癌细胞的增殖和侵袭，但减少细胞凋亡。PD-L1-lnc通过与c-Myc直接结合，增强c-Myc转录活性，在机制上促进肺腺癌的进展。结论PD-L1基因可通过选择性剪接产生长的非编码RNA，通过增强c-Myc活性促进肺腺癌的进展。我们的结果支持在肺癌治疗中结合PD-L1阻断来研究PD-L1-lnc的耗竭。
BackgroundAlthough using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear.ResultsEmploying qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity.ConclusionsIn summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.
登录
查看更多内容
仅使用序列信息预测RNA - 蛋白质相互作用。
影响因子：
3
作者：
Muppirala UK;Honavar VG;Dobbs D
通讯作者：
Dobbs D
DOI：
10.1093/bioinformatics/btt495
发表时间：
2013-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Agostini F;Zanzoni A;Klus P;Marchese D;Cirillo D;Tartaglia GG
通讯作者：
Tartaglia GG
影响因子：
64.8
作者：
Herbst RS;Soria JC;Kowanetz M;Fine GD;Hamid O;Gordon MS;Sosman JA;McDermott DF;Powderly JD;Gettinger SN;Kohrt HE;Horn L;Lawrence DP;Rost S;Leabman M;Xiao Y;Mokatrin A;Koeppen H;Hegde PS;Mellman I;Chen DS;Hodi FS
通讯作者：
Hodi FS
影响因子：
82.9
作者：
Cerezo, Michael;Guemiri, Ramdane;Robert, Caroline
通讯作者：
Robert, Caroline
影响因子：
11.5
作者：
Berger, Raanan;Rotem-Yehudar, Rinat;Nagler, Arnon
通讯作者：
Nagler, Arnon