Aerosolized miR-138-5p and miR-200c targets PD-L1 for lung cancer prevention.
Aerosolized miR-138-5p and miR-200c targets PD-L1 for lung cancer prevention.
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DOI：
10.3389/fimmu.2023.1166951
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发表时间：
2023
影响因子：
7.3
通讯作者：
You, Ming
中科院分区：
文献类型：
--
作者：
Zhang, Qi;Pan, Jing;Xiong, Donghai;Zheng, Junjun;McPherson, Kristi N.;Lee, Sangbeom;Huang, Mofei;Xu, Yitian;Chen, Shu-hsia;Wang, Yian;Ruiz, Lea Hildebrandt;You, Ming
发展能够防止肺部病变发展为恶性癌症的化学预防策略将降低这种致命疾病的死亡率和发病率。通过吸入递送microRNA（miRNA）是预防肺癌的新方法。在这项研究中，我们研究了雾化的miR-138- 5 p和miR-200 c miRNA模拟物在肺癌预防中的联合功效。两种miRNAs的组合抑制苯并（a）芘（B（a）P）诱导的肺腺瘤和N-亚硝基-三-氯乙基脲（NTCU）诱导的肺鳞状细胞癌，且没有可检测的副作用。使用单细胞RNA测序（scRNA-seq）和成像质谱细胞术（IMC），我们发现两种miRNA都抑制程序性细胞死亡配体1（PD-L1）的表达。我们的流式细胞术结果显示，组合的miRNA的雾化递送增加了CD 4+和CD 8 + T细胞，并降低了程序性细胞死亡蛋白1（PD-1）和T调节细胞的表达。我们的研究结果表明，靶向PD-L1的雾化microRNA的递送可以非常有效地预防小鼠肺癌的发展和进展。
The development of chemopreventive strategies with the ability to prevent the progression of lung lesions to malignant cancers would reduce the mortality and morbidity resulting from this deadly disease. Delivery of microRNA (miRNA) by inhalation is a novel method for lung cancer prevention. In this study, we investigated the combined efficacy of aerosolized miR-138-5p and miR-200c miRNA mimics in lung cancer prevention. Combination of the two miRNAs inhibited Benzo(a)pyrene (B((a))P)-induced lung adenomas and N-nitroso-tris-chloroethylurea (NTCU)-induced lung squamous cell carcinomas with no detectable side effects. Using single-cell RNA sequencing (scRNA-seq) and imaging mass cytometry (IMC), we found that both miRNAs inhibited programmed cell death ligand 1 (PD-L1) expression. Our flow cytometry results showed that aerosolized delivery of combined miRNAs increased CD4+ and CD8+ T cells and reduced the expression of programmed cell death protein 1 (PD-1) and T-regulatory cells. Our results demonstrated that the delivery of aerosolized microRNAs targeting PD-L1 can be highly effective in preventing lung cancer development and progression in mice.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
64.5
作者：
Levine JH;Simonds EF;Bendall SC;Davis KL;Amir el-AD;Tadmor MD;Litvin O;Fienberg HG;Jager A;Zunder ER;Finck R;Gedman AL;Radtke I;Downing JR;Pe'er D;Nolan GP
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Nolan GP
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
4.6
作者：
Pan J;Xiong D;Zhang Q;Szabo E;Miller MS;Lubet RA;Wang Y;You M
通讯作者：
You M
影响因子：
46.9
作者：
Risso, Davide;Ngai, John;Speed, Terence P.;Dudoit, Sandrine
通讯作者：
Dudoit, Sandrine