miR-142-5p regulates CD4+ T cells in human non-small cell lung cancer through PD-L1 expression via the PTEN pathway

Wan,Jun; Ling,Xiean; Peng,Bin; Ding,Guanggui

doi:10.3892/or.2018.6439

miR-142-5p regulates CD4+ T cells in human non-small cell lung cancer through PD-L1 expression via the PTEN pathway

Authors:
- Jun Wan
- Xiean Ling
- Bin Peng
- Guanggui Ding
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Affiliations: Department of Thoracic Surgery, The Shenzhen People's Hospital, The Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
Published online on: May 16, 2018 https://doi.org/10.3892/or.2018.6439
Pages: 272-282
Copyright: © Wan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to evaluate the function of microRNA (miR)-142-5p on cancer immunity to induce apoptosis in human non-small cell lung cancer (NSCLC) and its mechanism. miR-142-5p expression was upregulated, and CD4+ T cell levels were reduced in patients with NSCLC. Overexpression of miR-142-5p expression inhibited the cancer effects of CD4+ T cells on NSCLC cell lines, and downregulation of miR-142-5p increased the cancer effects of CD4+ T cells on NSCLC cell lines, compared with the control group. In addition, we found that overexpression of miR-142-5p suppressed PTEN protein expression and induced PI3K, p-Akt and PD-L1 protein expression in an in vitro model of NSCLC. Downregulation of miR-142-5p induced PTEN and PD-L1 protein expression and suppressed PI3K and p-Akt and protein expression in an in vitro model of NSCLC. The suppression of PD-L1 reduced the cancer effects of CD4+ T cells on NSCLC cell lines following miR-142-5p downregulation. The inhibition of PTEN also reduced the cancer effects of CD4+ T cells on NSCLC cell lines following miR-142-5p downregulation. Therefore, our study demonstrated that miR-142-5p regulated CD4+ T cells in human NSCLC through PD-L1 expression via the PTEN pathway.

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1	Song M, Chen D, Lu B, Wang C, Zhang J, Huang L, Wang X, Timmons CL, Hu J, Liu B, et al: PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer. PLoS One. 8:e658212013. View Article : Google Scholar : PubMed/NCBI
2	Atefi M, Avramis E, Lassen A, Wong DJ, Robert L, Foulad D, Cerniglia M, Titz B, Chodon T, Graeber TG, et al: Effects of MAPK and PI3K pathways on PD-L1 expression in melanoma. Clin Cancer Res. 20:3446–3457. 2014. View Article : Google Scholar : PubMed/NCBI
3	Zhao L, Li C, Liu F, Zhao Y, Liu J, Hua Y, Liu J, Huang J and Ge C: A blockade of PD-L1 produced antitumor and antimetastatic effects in an orthotopic mouse pancreatic cancer model via the PI3K/Akt/mTOR signaling pathway. Onco Targets Ther. 10:2115–2126. 2017. View Article : Google Scholar : PubMed/NCBI
4	Fujimoto N, Kubo T, Inatomi H, Bui HT, Shiota M, Sho T and Matsumoto T: Polymorphisms of the androgen transporting gene SLCO2B1 may influence the castration resistance of prostate cancer and the racial differences in response to androgen deprivation. Prostate Cancer Prostatic Dis. 16:336–340. 2013. View Article : Google Scholar : PubMed/NCBI
5	Sharifi N, Hamada A, Sissung T, Danesi R, Venzon D, Baum C, Gulley JL, Price DK, Dahut WL and Figg WD: A polymorphism in a transporter of testosterone is a determinant of androgen independence in prostate cancer. BJU Int. 102:617–621. 2008. View Article : Google Scholar : PubMed/NCBI
6	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
7	Cai W, Jiang H, Yu Y, Xu Y, Zuo W, Wang S and Su Z: miR-367 regulation of DOC-2/DAB2 interactive protein promotes proliferation, migration and invasion of osteosarcoma cells. Biomed Pharmacother. 95:120–128. 2017. View Article : Google Scholar : PubMed/NCBI
8	Talebi F, Ghorbani S, Chan WF, Boghozian R, Masoumi F, Ghasemi S, Vojgani M, Power C and Noorbakhsh F: MicroRNA-142 regulates inflammation and T cell differentiation in an animal model of multiple sclerosis. J Neuroinflammation. 14:552017. View Article : Google Scholar : PubMed/NCBI
9	Zhou G, Sprengers D, Boor PPC, Doukas M, Schutz H, Mancham S, Pedroza-Gonzalez A, Polak WG, de Jonge J, Gaspersz M, et al: Antibodies against immune checkpoint molecules restore functions of tumor-infiltrating T cells in hepatocellular carcinomas. Gastroenterology. 153:1107–1119.e10. 2017. View Article : Google Scholar : PubMed/NCBI
10	Yi H, Guo C, Yu X, Gao P, Qian J, Zuo D, Manjili MH, Fisher PB, Subjeck JR and Wang XY: Targeting the immunoregulator SRA/CD204 potentiates specific dendritic cell vaccine-induced T-cell response and antitumor immunity. Cancer Res. 71:6611–6620. 2011. View Article : Google Scholar : PubMed/NCBI
11	Hou PF, Zhu LJ, Chen XY and Qiu ZQ: Age-related changes in CD4⁺CD25⁺Foxp3⁺ regulatory T cells and their relationship with lung cancer. PLoS One. 12:e01730482017. View Article : Google Scholar : PubMed/NCBI
12	Kotsakis A, Koinis F, Katsarou A, Gioulbasani M, Aggouraki D, Kentepozidis N, Georgoulias V and Vetsika EK: Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients. Sci Rep. 6:392472016. View Article : Google Scholar : PubMed/NCBI
13	Lee TM, Lin SZ and Chang NC: Antiarrhythmic effect of lithium in rats after myocardial infarction by activation of Nrf2/HO-1 signaling. Free Radic Biol Med. 77:71–81. 2014. View Article : Google Scholar : PubMed/NCBI
14	Liu H, Carvalhais LC, Kazan K and Schenk PM: Development of marker genes for jasmonic acid signaling in shoots and roots of wheat. Plant Signal Behav. 11:e11766542016. View Article : Google Scholar : PubMed/NCBI
15	Zhao H, Chai W, Gao W, Xu L, Zhang H and Yang Y: Hyperoxygenated solution: Effects on acute hypobaric hypoxia-induced oxidative damage in rabbits. High Alt Med Biol. 10:283–291. 2009. View Article : Google Scholar : PubMed/NCBI
16	Gao C, Zhang G, Sun X, Zhang H, Kuai J, Zhao H, Yao L, Yu D, Yang Y, Xu L, et al: The effects of intravenous hyperoxygenated solution infusion on systemic oxygenation and intrapulmonary shunt during one-lung ventilation in pigs. J Surg Res. 159:653–659. 2010. View Article : Google Scholar : PubMed/NCBI
17	Karu I, Loit R, Zilmer K, Kairane C, Paapstel A, Zilmer M and Starkopf J: Pre-treatment with hyperoxia before coronary artery bypass grafting - effects on myocardial injury and inflammatory response. Acta Anaesthesiol Scand. 51:1305–1313. 2007. View Article : Google Scholar : PubMed/NCBI
18	Dumitriu IE, Dunbar DR, Howie SE, Sethi T and Gregory CD: Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma cells and prime the differentiation of CD4⁺CD25⁺Foxp3⁺ regulatory T cells. J Immunol. 182:2795–2807. 2009. View Article : Google Scholar : PubMed/NCBI
19	Bai X, Zhou Y, Chen P, Yang M and Xu J: MicroRNA-142-5p induces cancer stem cell-like properties of cutaneous squamous cell carcinoma via inhibiting PTEN. J Cell Biochem. 119:2179–2188. 2018. View Article : Google Scholar : PubMed/NCBI
20	Gong X, Li X, Jiang T, Xie H, Zhu Z, Zhou F and Zhou C: Combined radiotherapy and anti-PD-L1 antibody synergistically enhances antitumor effect in non-small cell lung cancer. J Thorac Oncol. 12:1085–1097. 2017. View Article : Google Scholar : PubMed/NCBI
21	Lee SY, Jung DK, Choi JE, Jin CC, Hong MJ, Do SK, Kang HG, Lee WK, Seok Y, Lee EB, et al: Functional polymorphisms in PD-L1 gene are associated with the prognosis of patients with early stage non-small cell lung cancer. Gene. 599:28–35. 2017. View Article : Google Scholar : PubMed/NCBI
22	Jia L, Xi Q, Wang H, Zhang Z, Liu H, Cheng Y, Guo X, Zhang J, Zhang Q, Zhang L, et al: miR-142-5p regulates tumor cell PD-L1 expression and enhances anti-tumor immunity. Biochem Biophys Res Commun. 488:425–431. 2017. View Article : Google Scholar : PubMed/NCBI
23	Zhang Y, Liu Z, Tian M, Hu X, Wang L, Ji J and Liao A: The altered PD-1/PD-L1 pathway delivers the ‘one-two punch’ effects to promote the Treg/Th17 imbalance in pre-eclampsia. Cell Mol Immunol. Sep 11–2017.(Epub ahead of print). View Article : Google Scholar :
24	Li QS, Meng FY, Zhao YH, Jin CL, Tian J and Yi XJ: Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells. Bone Joint Res. 6:464–471. 2017. View Article : Google Scholar : PubMed/NCBI
25	Pressler H, Sissung TM, Venzon D, Price DK and Figg WD: Expression of OATP family members in hormone-related cancers: Potential markers of progression. PLoS One. 6:e203722011. View Article : Google Scholar : PubMed/NCBI
26	Liu L, Gao H, Wang H, Zhang Y, Xu W, Lin S, Wang H, Wu Q and Guo J: Catalpol promotes cellular apoptosis in human HCT116 colorectal cancer cells via microRNA-200 and the downregulation of PI3K-Akt signaling pathway. Oncol Lett. 14:3741–3747. 2017. View Article : Google Scholar : PubMed/NCBI