Comparative Expression Profile Analysis of Apoptosis-Related miRNA and Its Target Gene in Leishmania major Infected Macrophages
-
Zohreh LASJERDI
,
Hossein GHANBARIAN
,
Samira MOHAMMADI YEGANEH
,
Seyyed Javad SEYYED TABAEI
,
Mehdi MOHEBALI
,
Niloofar TAGHIPOUR
,
Ameneh KOOCHAKI
,
Faezeh HAMIDI
,
Mostafa GHOLAMREZAEI
,
Ali HAGHIGHI
Abstract
Background: Cutaneous Leishmaniasis (CL) is an emerging uncontrollable and neglected infectious disease worldwide including Iran. The aim of this study was to investigate the expression profile of apoptosis- related miRNA and its target gene in macrophages.
Methods: This study was carried out in the Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran from January 2016 to November 2018. Applying literature reviews, bioinformatics software, and microarray expression analysis, we selected miRNA-24-3p interfering in apoptosis pathway. The expression profile of this miRNA and target gene were investigated in Leishmania major (MRHO/IR/75/ER)-infected primary and RAW 264.7 macrophages (IBRC-C10072) compared with non-infected macrophages (control group) using quantitative Real-time PCR.
Results: Results of bioinformatics analysis showed that miR-24-3p as anti-apoptotic miRNA inhibits pro-apoptotic genes (Caspases 3 and 7). Microarray expression data presented in Gene Expression Omnibus (GEO) revealed a significant difference in the expression level of selected miRNA and its target gene between two groups. QRT-PCR results showed that the expression of miR-24-3p was upregulated in L. major infectioned macrophages that approved the results of bioinformatics and microarray analysis.
Conclusion: Parasite can alter miRNAs expression pattern in the host cells to establish infection and its survival. Alteration in miRNAs levels likely plays an important role in regulating macrophage functions following L. major infection. These results could highlight current understanding and new insights concerning the gene expression in macrophages during leishmaniasis and will help to development of novel strategies for control and treatment of CL.
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9. Gholamrezaei M, Mohebali M, Hanafi-Bojd AA, et al. Ecological Niche Modeling of main reservoir hosts of zoonotic cutaneous leishmaniasis in Iran. Acta Trop. 2016; 160:44-52.
10. Khanjani N, González U, Leonardi-Bee J, et al. Vaccines for preventing cutaneous leishmaniasis. Cochrane Database Syst Rev. 2018(1); CD007634.
11. Henry JC, de Vries Sophia H, Reedijk Henk DFH, et al. Cutaneous Leishmaniasis: Recent Develop-ments in Diagnosis and Management. Am J Clin Dermatol. 2015; 16(2):99-109.
12. Santos DO, Coutinho CE, Madeira MF, et al. Leishmaniasis treatment -A challenge that remains: A review. Parasitol Res. 2004; 103(1):1-10.
13. Croft SL, Olliaro P. Leishmaniasis chemotherapy-challenges and opportunities. Clin Microbiol Infect. 2011; 17(10):1478-83.
14. Rojas R, Valderrama L, Valderrama M, et al.Resistance to Antimony and Treatment Failure in Human Leishmania (Viannia) Infection. J Infect Dis. 2006; 193:1375-83.
15. Mohebali M, Kazemirad E, Hajjaran H, et al. Gene expression analysis of antimony resistance in Leish-mania tropica using quantitative real-time PCR fo-cused on genes involved in trypanothione metabo-lism and drug transport. Arch Dermatol Res. 2019; (1):9-17.
16. Paris C, M.Loiseau P, Bories C, et al. Miltefosine Induces Apoptosis-Like Death in Leishmania donovani Promastigotes. Antimicrob Agents Chemother. 2004; 48(3):852-9.
17. Khademvatan S, Gharavi MJ, Rahim F, et al. Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains. Korean J Para-sitol. 2011; 49(1):17-23.
18. Sen R, Bandyopadhyay S, Dutta A, et al. Artemis-inin triggers induction of cell-cycle arrest and apop-tosis in Leishmania donovani promastigotes. J Med Microbiol. 2007; 56(9):1213-18.
19. White E. Life, death and the pursuit of apoptosis. Genes Dev. 1996; 10(1):1-15.
20. Thompson CB. Apoptosis in the pathogenesis and treatment of diseases. Science.1995; 267(5203):1456-62.
21. Ameisen, J. C. On the origin, evolution, and nature of programmed cell death: a timeline of four billion years. Cell Death Differ. 2002; 9:367-93.
22. Thornberry NA, and Lazebnik, Y. Caspases: ene-mies within. Science.1998; 281(5381):1312-6.
23. Zhenyi Su, Zuozhang Y, Yongqing Xu, et al. Mi-croRNAs in apoptosis, autophagy and necroptosis. Oncotarget. 2015; 6(11):8474-90.
24. Krol J, Loedige I, Filipowicz W. The widespread regula¬tion of microRNA biogenesis, function and decay. Nat Rev Genet. 2010; 11(9):597-610.
25. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97.
26. Lemaire J, Mkannez G, Guerfali FZ, et al. Mi-croRNA Expression Profile in Human macro-phages in Response to Leishmania major Infection. PLoS Negl Trop Dis. 2013; 7(10).
27. Tiwari N, Kumar V, Gedda MR, et al. Identification and characterization of miRNAs in response to Leishmania donovani infection: delineation of their roles in macrophage dysfunction. Front Microbiol. 2017; 8(314):1-11.
28. Geraci NS,Tan JC, Mcdowell MA. Characterization of microRNA expression profiles in Leishmania in-fected human phagocytes. Parasite Immunol. 2015; 37:43-51.
29. Olivier M, Gregory D, and Forget G. Subversion Mechanisms by Which Leishmania Parasites Can Escape the Host Immune Response: a Signaling Point of View. Clin Microbiol Rev. 2005; 18(2):293-305.
30. Soong L. Modulation of dendritic cell function by Leishmania parasites. J Immunol. 2008; 180:4355-60.
31. Muxel SM, Laranjeira-Silva MF, Zampieri RA, et al. Leishmania (Leishmania) amazonensis induces macro-phage miR-294 and miR-721 expression and modu-lates infection by targeting NOS2 and L-arginine metabolism. Sci Rep. 2017; 7.
32. Zhang X, Goncalves R, and M. Moser D. The Isolation and Characterization of Murine macro-phages. Curr Protoc Immunol. 2008; chapter: Unit 14.1.
33. Livak KJ and Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) Method. Meth-ods. 2001; 25(4):402-8.
34. Tsang WP, Kwok TT. Let-7a microRNA sup-presses therapeutics-induced cancer cell death by targeting caspase-3. Apoptosis. 2008; 13(10):1215-22.
35. Fang J, Song X-W, Tian J, et al. Overexpression of microRNA-378 attenuates ischemia-induced apop-tosis by inhibiting caspase-3 expression in cardiac myocytes. Apoptosis. 2012; 17(4):410-23.
36. Daszak P, Cunningham AA, Hyatt AD. Anthropo-genic environmental change and the emergence of infectious diseases in wildlife. Acta Trop. 2001; 78(2):103-16.
37. Murray HW, Berman JD, Davies CR, et al. Ad-vances in leishmaniasis. Lancet. 2005; 366(9496):1561-77.
38. Mohebali M, Javadian E, Yaghoobi-Ershadi MR, et al. Characterization of Leishmania infection in ro-dents from endemic areas of the Islamic Republic of Iran. East Mediterr Health J. 2004; 10(4-5):591-9.
39. Rabhi I, Rabhi1 S, Ben-Othman R, et al. Tran-scriptomic Signature of Leishmania Infected Mice Macrophages: A Metabolic Point of View. PLoS Negl Trop Dis. 2012; 6(8):e1763.
40. Jia B, Chang Z, Wei X, et al. Plasma microRNAs are promising novel biomarkers for the early detec-tion of Toxoplasma gondii infection. Parasit Vectors. 2014; 7(433).
41. Manzano-Roman R, Siles-Lucas M. MicroRNAs in parasitic diseases: Potential for diagnosis and target-ing. Mol Biochem Parasitol.2012; 186:81-6.
42. Chaussabel D, Semnani RT, McDowell MA, et al. Unique gene expression profiles of human macro-phages and dendritic cells to phylogenetically dis-tinct parasites. Blood. 2003; 102:672-81.
43. Buates S, Matlashewski G. General suppression of macrophage gene expression during Leishmania do-novani infection. J Immunol.2001; 166:3416-22.
44. Zeiner GM, Norman KL, Thomson JM, et al. Toxoplasma gondii infection specifically increases the levels of key host microRNAs. PLoS One. 2010:5(1):e8742.
45. Cimmino A, Calin GA, Fabbri M, V, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005; (102)39: 13944-9.
46. De Santis R, Liepelt A, C. Mossanen J, et al. miR-155 targets Caspase-3 mRNA in activated macro-phages. RNA Biol. 2016; 13(1):43-58.
2. Alvar J, Vélez ID, Bern C, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012; 7(5).
3. Desjeux P. Human leishmaniases: epidemiology and public health aspects. World Health Stat Q. 1992; 45:267-75.
4. Hepburn NC. Cutaneous leishmaniasis: current and future management. Expert Rev Anti Infect Ther. 2003; 1(4):563-70.
5. World Health Organization (WHO). Control of the leishmaniasis Report of a Meeting of the WHO Export Committee on the Control of Leishmania-sis, WHO Technical Report Series 949, 2010; 1-187.
6. Sharifi I, Aflatoonian MR, Fekri AR, et al. A Com-prehensive Review of Cutaneous Leishmaniasis in Kerman Province, Southeastern Iran- Narrative Review Article. Iran J Public Health. 2015; 44(3):299-307.
7. Hezari F, Niyyati M, Seyyed Tabaei SJ, et al. Fre-quency of Cutaneous Leishmaniasis and Species Identification in Suspected Individuals from Goles-tan Province, Northern Iran in 2014. Iran J Public Health. 2016; 45(10):1348-54.
8. Holakouie-Naienia K, Mostafavib E, Darvishi Bo-looranic A, et al. Spatial modeling of cutaneous leishmaniasis in Iran from 1983 to 2013. Acta Trop. 2017; 166:67-73.
9. Gholamrezaei M, Mohebali M, Hanafi-Bojd AA, et al. Ecological Niche Modeling of main reservoir hosts of zoonotic cutaneous leishmaniasis in Iran. Acta Trop. 2016; 160:44-52.
10. Khanjani N, González U, Leonardi-Bee J, et al. Vaccines for preventing cutaneous leishmaniasis. Cochrane Database Syst Rev. 2018(1); CD007634.
11. Henry JC, de Vries Sophia H, Reedijk Henk DFH, et al. Cutaneous Leishmaniasis: Recent Develop-ments in Diagnosis and Management. Am J Clin Dermatol. 2015; 16(2):99-109.
12. Santos DO, Coutinho CE, Madeira MF, et al. Leishmaniasis treatment -A challenge that remains: A review. Parasitol Res. 2004; 103(1):1-10.
13. Croft SL, Olliaro P. Leishmaniasis chemotherapy-challenges and opportunities. Clin Microbiol Infect. 2011; 17(10):1478-83.
14. Rojas R, Valderrama L, Valderrama M, et al.Resistance to Antimony and Treatment Failure in Human Leishmania (Viannia) Infection. J Infect Dis. 2006; 193:1375-83.
15. Mohebali M, Kazemirad E, Hajjaran H, et al. Gene expression analysis of antimony resistance in Leish-mania tropica using quantitative real-time PCR fo-cused on genes involved in trypanothione metabo-lism and drug transport. Arch Dermatol Res. 2019; (1):9-17.
16. Paris C, M.Loiseau P, Bories C, et al. Miltefosine Induces Apoptosis-Like Death in Leishmania donovani Promastigotes. Antimicrob Agents Chemother. 2004; 48(3):852-9.
17. Khademvatan S, Gharavi MJ, Rahim F, et al. Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains. Korean J Para-sitol. 2011; 49(1):17-23.
18. Sen R, Bandyopadhyay S, Dutta A, et al. Artemis-inin triggers induction of cell-cycle arrest and apop-tosis in Leishmania donovani promastigotes. J Med Microbiol. 2007; 56(9):1213-18.
19. White E. Life, death and the pursuit of apoptosis. Genes Dev. 1996; 10(1):1-15.
20. Thompson CB. Apoptosis in the pathogenesis and treatment of diseases. Science.1995; 267(5203):1456-62.
21. Ameisen, J. C. On the origin, evolution, and nature of programmed cell death: a timeline of four billion years. Cell Death Differ. 2002; 9:367-93.
22. Thornberry NA, and Lazebnik, Y. Caspases: ene-mies within. Science.1998; 281(5381):1312-6.
23. Zhenyi Su, Zuozhang Y, Yongqing Xu, et al. Mi-croRNAs in apoptosis, autophagy and necroptosis. Oncotarget. 2015; 6(11):8474-90.
24. Krol J, Loedige I, Filipowicz W. The widespread regula¬tion of microRNA biogenesis, function and decay. Nat Rev Genet. 2010; 11(9):597-610.
25. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97.
26. Lemaire J, Mkannez G, Guerfali FZ, et al. Mi-croRNA Expression Profile in Human macro-phages in Response to Leishmania major Infection. PLoS Negl Trop Dis. 2013; 7(10).
27. Tiwari N, Kumar V, Gedda MR, et al. Identification and characterization of miRNAs in response to Leishmania donovani infection: delineation of their roles in macrophage dysfunction. Front Microbiol. 2017; 8(314):1-11.
28. Geraci NS,Tan JC, Mcdowell MA. Characterization of microRNA expression profiles in Leishmania in-fected human phagocytes. Parasite Immunol. 2015; 37:43-51.
29. Olivier M, Gregory D, and Forget G. Subversion Mechanisms by Which Leishmania Parasites Can Escape the Host Immune Response: a Signaling Point of View. Clin Microbiol Rev. 2005; 18(2):293-305.
30. Soong L. Modulation of dendritic cell function by Leishmania parasites. J Immunol. 2008; 180:4355-60.
31. Muxel SM, Laranjeira-Silva MF, Zampieri RA, et al. Leishmania (Leishmania) amazonensis induces macro-phage miR-294 and miR-721 expression and modu-lates infection by targeting NOS2 and L-arginine metabolism. Sci Rep. 2017; 7.
32. Zhang X, Goncalves R, and M. Moser D. The Isolation and Characterization of Murine macro-phages. Curr Protoc Immunol. 2008; chapter: Unit 14.1.
33. Livak KJ and Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) Method. Meth-ods. 2001; 25(4):402-8.
34. Tsang WP, Kwok TT. Let-7a microRNA sup-presses therapeutics-induced cancer cell death by targeting caspase-3. Apoptosis. 2008; 13(10):1215-22.
35. Fang J, Song X-W, Tian J, et al. Overexpression of microRNA-378 attenuates ischemia-induced apop-tosis by inhibiting caspase-3 expression in cardiac myocytes. Apoptosis. 2012; 17(4):410-23.
36. Daszak P, Cunningham AA, Hyatt AD. Anthropo-genic environmental change and the emergence of infectious diseases in wildlife. Acta Trop. 2001; 78(2):103-16.
37. Murray HW, Berman JD, Davies CR, et al. Ad-vances in leishmaniasis. Lancet. 2005; 366(9496):1561-77.
38. Mohebali M, Javadian E, Yaghoobi-Ershadi MR, et al. Characterization of Leishmania infection in ro-dents from endemic areas of the Islamic Republic of Iran. East Mediterr Health J. 2004; 10(4-5):591-9.
39. Rabhi I, Rabhi1 S, Ben-Othman R, et al. Tran-scriptomic Signature of Leishmania Infected Mice Macrophages: A Metabolic Point of View. PLoS Negl Trop Dis. 2012; 6(8):e1763.
40. Jia B, Chang Z, Wei X, et al. Plasma microRNAs are promising novel biomarkers for the early detec-tion of Toxoplasma gondii infection. Parasit Vectors. 2014; 7(433).
41. Manzano-Roman R, Siles-Lucas M. MicroRNAs in parasitic diseases: Potential for diagnosis and target-ing. Mol Biochem Parasitol.2012; 186:81-6.
42. Chaussabel D, Semnani RT, McDowell MA, et al. Unique gene expression profiles of human macro-phages and dendritic cells to phylogenetically dis-tinct parasites. Blood. 2003; 102:672-81.
43. Buates S, Matlashewski G. General suppression of macrophage gene expression during Leishmania do-novani infection. J Immunol.2001; 166:3416-22.
44. Zeiner GM, Norman KL, Thomson JM, et al. Toxoplasma gondii infection specifically increases the levels of key host microRNAs. PLoS One. 2010:5(1):e8742.
45. Cimmino A, Calin GA, Fabbri M, V, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005; (102)39: 13944-9.
46. De Santis R, Liepelt A, C. Mossanen J, et al. miR-155 targets Caspase-3 mRNA in activated macro-phages. RNA Biol. 2016; 13(1):43-58.
| Files | ||
| Issue | Vol 15 No 3 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v15i3.4197 | |
| Keywords | ||
| Apoptosis In vitro Leishmania major Macrophage MicroRNAs | ||
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How to Cite
1.
LASJERDI Z, GHANBARIAN H, MOHAMMADI YEGANEH S, SEYYED TABAEI SJ, MOHEBALI M, TAGHIPOUR N, KOOCHAKI A, HAMIDI F, GHOLAMREZAEI M, HAGHIGHI A. Comparative Expression Profile Analysis of Apoptosis-Related miRNA and Its Target Gene in Leishmania major Infected Macrophages. Iran J Parasitol. 2020;15(3):332-340.
