miR-155 is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO3

Huang,Jian; Jiao,Junhua; Xu,Weihua; Zhao,Huayang; Zhang,Chunxiao; Shi,Yan; Xiao,Zhijian

doi:10.3892/mmr.2015.4250

miR-155 is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO3

Authors:
- Jian Huang
- Junhua Jiao
- Weihua Xu
- Huayang Zhao
- Chunxiao Zhang
- Yan Shi
- Zhijian Xiao
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Affiliations: Second Tuberculosis Internal Medicine Department, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, First Tuberculosis Internal Medicine Department, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Third Tuberculosis Internal Medicine Department, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
Published online on: August 25, 2015 https://doi.org/10.3892/mmr.2015.4250
Pages: 7102-7108

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Abstract

The aim of the present study was to investigate the association between microRNA (miR)-155 and apoptosis of monocytes infected by Mycobacterium tuberculosis, to examine the effect of forkhead box O3 (FOXO3) on miR‑155. The present study analysed the apoptosis of CD14+ in the peripheral blood of patients with active tuberculosis, disposed the THP‑1 human monocytic cell line by BCG and examined the expression of miR‑155. Furthermore, the expression of FOXO3 in THP‑1 cells was determined, and wild- and mutant-type luciferase reporter plasmids containing FOXO3 3'‑untranslated regions (UTRs) were constructed to analyse the expression of luciferase. Finally, an over‑expression plasmid was constructed, and THP-1 cells were transfected with control miRNA, miR‑155 and the plasmid, which revealed that miR‑155 inhibited the apoptosis of THP‑1 cells. miR‑155 in the THP‑1 cells infected by BCG was upregulated and apoptosis also increased. However, the apoptosis declined when the cells were transfected with the control miRNA and miR‑155. Folllowing transfection with miR‑155, the expression of FOXO3 decreased. Transfection with miR‑155 and the FOXO3 3'-UTRs significantly reduced luciferase, and overexpression of FOXO3 reversed the inhibitory role of miR‑155. From these results, it was concluded that mycobacteria can improve the level of miR‑155, while BCG can induce apoptosis in THP‑1 cells. The results suggested FOXO3 is a downstream target gene of miR‑155, which combines 3'-UTRs to inhibit the expression of FOXO3.

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1	WHO: Global tuberculosis report. World Health Organization; France: pp. 1–89. 2012
2	Cooper AM: Cell-mediated immune responses in tuberculosis. Annu Rev Immunol. 27:393–422. 2009. View Article : Google Scholar : PubMed/NCBI
3	Natarajan K, Kundu M, Sharma P and Basu J: Innate immune responses to M. tuberculosis infection. Tuberculosis (Edinb). 91:427–431. 2011. View Article : Google Scholar
4	Smith I: Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbiol Rev. 16:463–496. 2003. View Article : Google Scholar : PubMed/NCBI
5	Russell DG, Barry CE III and Flynn JL: Tuberculosis: What we don't know can and does, hurt us. Science. 328:852–856. 2010. View Article : Google Scholar : PubMed/NCBI
6	Riendeau CJ and Kornfeld H: THP-1 cell apoptosis in response to Mycobacterial infection. Infect Immun. 71:254–259. 2003. View Article : Google Scholar :
7	Khalilullah SA, Harapan H, Hasan N, Winardi W, Ichsan I and Mulyadi M: Host genome polymorphisms and tuberculosis infection: What we have to say? Egyptian Journal of Chest Diseases and Tuberculosis. 63:173–85. 2014. View Article : Google Scholar
8	Akita T, Takuno S and Innan H: Modeling evolutionary growth of a microRNA-mediated regulation system. J Theor Biol. 311:54–65. 2012. View Article : Google Scholar : PubMed/NCBI
9	Kanwar JR, Mahidhara G and Kanwar RK: MicroRNA in human cancer and chronic inflammatory diseases. Front Biosci (Schol Ed). 2:1113–1126. 2010.
10	Chen XM: MicroRNA signatures in liver diseases. World J Gastroenterol. 15:1665–1672. 2009. View Article : Google Scholar : PubMed/NCBI
11	Christensen M and Schratt GM: MicroRNA involvement in developmental and functional aspects of the nervous system and in neurological diseases. Neurosci Lett. 466:55–62. 2009. View Article : Google Scholar : PubMed/NCBI
12	Pauley KM, Cha S and Chan EK: MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun. 32:189–194. 2009. View Article : Google Scholar : PubMed/NCBI
13	Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, et al: Requirement of bic/microRNA-155 for normal immune function. Science. 316:608–611. 2007. View Article : Google Scholar : PubMed/NCBI
14	Curtale G, Citarella F, Carissimi C, Goldoni M, Carucci N, Fulci V, Franceschini D, Meloni F, Barnaba V and Macino G: An emerging player in the adaptive immune response: MicroRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood. 115:265–273. 2010. View Article : Google Scholar
15	Liu Y, Wang X, Jiang J, Cao Z, Yang B and Cheng X: Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis. Mol Immunol. 48:1084–1090. 2011. View Article : Google Scholar : PubMed/NCBI
16	Marín ND, París SC, Rojas M and García LF: Reduced frequency of memory T cells and increased Th17 responses in patients with active tuberculosis. Clin Vaccine Immunol. 19:1667–1676. 2012. View Article : Google Scholar : PubMed/NCBI
17	Tsitsiou E and Lindsay MA: MicroRNAs and the immune response. Curr Opin Pharmacol. 9:514–520. 2009. View Article : Google Scholar : PubMed/NCBI
18	Hu R, Kagele DA, Huffaker TB, Runtsch MC, Alexander M, Liu J, Bake E, Su W, Williams MA, Rao DS, et al: miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation. Immunity. 41:605–619. 2014. View Article : Google Scholar : PubMed/NCBI
19	Rajaram MV, Ni B, Morris JD, Brooks MN, Carlson TK, Bakthavachalu B, Schoenberg DR, Torrelles JB and Schlesinger LS: Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b. Proc Natl Acad Sci USA. 108:17408–17413. 2011. View Article : Google Scholar : PubMed/NCBI
20	Bala S, Marcos M, Kodys K, Csak T, Catalano D, Mandrekar P and Szabo G: Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease. J Biol Chem. 286:1436–1444. 2011. View Article : Google Scholar :
21	Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J and Greenberg ME: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 96:857–868. 1999. View Article : Google Scholar : PubMed/NCBI
22	Arden KC: FOXO animal models reveal a variety of diverse roles for FOXO transcription factors. Oncogene. 27:2345–2350. 2008. View Article : Google Scholar : PubMed/NCBI
23	Peng SL: Foxo in the immune system. Oncogene. 27:2337–2344. 2008. View Article : Google Scholar : PubMed/NCBI
24	Ticchioni M, Essafi M, Jeandel PY, Davi F, Cassuto JP, Deckert M and Bernard A: Homeostatic chemokines increase survival of B-chronic lymphocytic leukemia cells through inactivation of transcription factor FOXO3a. Oncogene. 26:7081–7091. 2007. View Article : Google Scholar : PubMed/NCBI
25	Haoues M, Refai A, Mallavialle A, Barbouche MR, Laabidi N, Deckert M and Essafi M: Forkhead box O3 (FOXO3) transcription factor mediates apoptosis in BCG-infected macrophages. Cell Microbiol. 16:1378–1390. 2014. View Article : Google Scholar : PubMed/NCBI
26	Harada Y, Harada Y, Elly C, Ying G, Paik JH, DePinho RA and Liu YC: Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells. J Exp Med. 207:1381–1391. 2010. View Article : Google Scholar : PubMed/NCBI
27	Ling N, Gu J, Lei Z, Li M, Zhao J, Zhang HT and Li X: MicroRNA-155 regulates cell proliferation and invasion by targeting FOXO3a in glioma. Oncol Rep. 30:2111–2118. 2013.PubMed/NCBI
28	Zhang L, Liu S, Zhang L, You H, Huang R, Sun L, He P, Chen S, Zhang H and Xie P: Real-time qPCR identifies suitable reference genes for Borna disease virus-infected rat cortical neurons. Int J Mol Sci. 15:21825–21839. 2014. View Article : Google Scholar : PubMed/NCBI
29	Liu Y, Jiang J, Wang X, Zhai F and Cheng X: MiR-582-5p is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO1. PloS One. 8:e783812013. View Article : Google Scholar : PubMed/NCBI
30	Wu J, Lu C, Diao N, et al: Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: A preliminary study. Hum Immunol. 73:31–37. 2012. View Article : Google Scholar