Altered Expression Levels of MicroRNA-155 and SOCS-1 in Peripheral Blood Mononuclear Cells of Newly Diagnosed Breast Cancer Patients
Abstract
MicroRNA-155 (miR-155) has a critical role in pro-inflammatory activation and tumor progression. In addition, miR-155 has various oncogenic effects in the tumor microenvironment by targeting the suppressor gene of cytokine signaling-1(SOCS-1) and interleukin-6 (IL-6). This study investigated the association of inflammatory changes with the variations of miR-155 expression in newly diagnosed breast cancer (NDBC) patients.
Seventy NDBC patients were categorized as lobular and ductal subgroups and forty healthy individuals participated in this study. The expression rate of miR-155 and its downstream target gene, SOCS-1, as well as the plasma levels of IL-6, were evaluated in peripheral blood mononuclear cells of NDBC patients; using real-time PCR and enzyme-linked immunosorbent assay, respectively.
Our results indicated an over-expression of miR-155 in the PBMCs of NDBC patients which was significantly associated with the tumor grade and the type of ductal carcinoma. In contrast, a significant downregulation of SOCS-1 was observed in NDBC patients compared to control group, however, there was no significant difference between two subtypes of BC. Furthermore, a higher concentration of plasma IL-6 was detected in NDBC patients compared to the healthy control group which had an inverse correlation with the SOCS-1 levels.
According to the potential effects of miR-155 on regulating the expression of SOCS-1 and IL-6, we suggest this small transcript as a promising diagnostic marker for various types of BC patients.
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal AJCacjfc. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.Cancer J Clin. 2018;68(6):394-424.
2. Reznikov AJEo. Hormonal impact on tumor growth and progression. Exp Oncol. 2015;37(3):162-72.
3. Moore HC, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015;372(10):923-32.
4. Li CI, Daling JR, Porter PL, Tang MTC, Malone KEJCr. Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor–Specific Subtypes of Contralateral Breast Cancer. Cancer Res. 2009;69(17):6865-70.
5. Zhu W, Qin W, Atasoy U, Sauter ERJBrn. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes. 2009;2(1):1-5.
6. Zhao C, Sun X, Li LJE. Biogenesis and function of extracellular miRNAs. ExRNA. 2019;1(1):1-9.
7. Faraoni I, Antonetti FR, Cardone J, BonmassarEJBeBA-MBoD. miR-155 gene: a typical multifunctional microRNA. BiochimBiophys Acta Gene Regul Mech. 2009;1792(6):497-505.
8. Vanni I, Alama A, Grossi F, Dal Bello MG, Coco SJDDT. Exosomes: a new horizon in lung cancer. Drug Discov Today. 2017;22(6):927-36.
9. Gillespie P, Ladame S, O'Hare DJA. Molecular methods in electrochemical microRNA detection. Anal. 2019;144(1):114-9.
10. Meseure D, DrakAlsibai K, Nicolas A, Bieche I, MorillonAJBri. Long noncoding RNAs as new architects in cancer epigenetics, prognostic biomarkers, and potential therapeutic targets. Biomed Res Int.2015;2015:320214.
11. Tomar D, Yadav AS, Kumar D, Bhadauriya G, Kundu GCJBeBA-GRM. Non-coding RNAs as potential therapeutic targets in breast cancer. BiochimBiophys Acta Gene Regul Mech.2020;1863(4):194378-9.
12. Nobili L, Ronchetti D, Taiana E, Neri AJO. Long non-coding RNAs in B-cell malignancies: a comprehensive overview. Oncotarget. 2017;8(36):60605.
13. Xia S, Feng J, Lei L, Hu J, Xia L, Wang J, et al. Comprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes. Brief Bioinform. 2017;18(6):984-92.
14. Witten LW, Cheng CJ, Slack FJJO. miR-155 drives oncogenesis by promoting and cooperating with mutations in the c-Kit oncogene. Oncogene. 2019;38(12):2151-61.
15. Jiang M, Zhang W-w, Liu P, Yu W, Liu T, Yu JJFii. Dysregulation of SOCS-mediated negative feedback of cytokine signaling in carcinogenesis and its significance in cancer treatment. Front Immunol. 2017;8:70.
16. Dudda JC, Salaun B, Ji Y, Palmer DC, Monnot GC, Merck E, et al. MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer. Immunity. 2013;38(4):742-53.
17. Yoshimura A, Ito M, Chikuma S, Akanuma T, NakatsukasaHJCSHpib. Negative regulation of cytokine signaling in immunity. Cold Spring HarbPerspect Biol. 2018;10(7):a028571.
18. Gershovich P, Karabelskii A, Ulitin A, Ivanov RJB. The role of checkpoint inhibitors and cytokines in adoptive cell-based cancer immunotherapy with genetically modified T cells. Biochem. 2019;84(7):695-710.
19. Korneev KV, Atretkhany K-SN, Drutskaya MS, Grivennikov SI, Kuprash DV, Nedospasov SAJC. TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis. Cytokine. 2017;89(12):127-35.
20. Li J, Mo H-Y, Xiong G, Zhang L, He J, Huang Z-F, et al. Tumor microenvironment macrophage inhibitory factor directs the accumulation of interleukin-17-producing tumor-infiltrating lymphocytes and predicts favorable survival in nasopharyngeal carcinoma patients. J Biol Chem. 2012;287(42):35484-95.
21. Xie G, Yao Q, Liu Y, Du S, Liu A, Guo Z, et al. IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures. Int J Oncol. 2012;40(4):1171-9.
22. Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, et al. Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PloS one. 2012;7:e47003.
23. Cortez MA, Welsh JW, Calin GA. Circulating microRNAs as noninvasive biomarkers in breast cancer. Minimal residual disease and circulating tumor cells in breast cancer: Springer. 2012;14(3):151-61.
24. Fuksiewicz M, Kowalska M, Kotowicz B, Rubach M, Chechlinska M, Pienkowski T, et al. Serum soluble tumour necrosis factor receptor type I concentrations independently predict prognosis in patients with breast cancer. Clin Chem Lab Med. 2010;48(10):1481-6.
25. Bousoik E, MontazeriAliabadiHJFio. “Do we know jack” about JAK? A closer look at JAK/STAT signaling pathway. Front Oncol. 2018;8(2):287.
26. Tanaka T, Narazaki M, KishimotoTJCSHpib. IL-6 in inflammation, immunity, and disease. Cold Spring HarbPerspect Biol. 2014;6(10):a016295.
27. Asroel EM.PengaruhPemberianMaduTerhadapPerubahan Kadar Soluble Fms-Like Tyrosine Kinase (Sflt-1), Soluble Endoglin (Seng), Vascular Endothelial Growth Factor (Vegf), Placental Growth Factor (Plgf), Tumor Necrosis Factor Alpha (Tnf-Α), Dan Interleukin 6 (Il-6) Pada Tikus Model Preeklamsia. repositori.usu.ac.id. 2020.
28. Xiao-juan MY-cD, Feng-xia LH-lCJAAS. Tumorigenic effect of interleukin-6 on mice with pancreatic carcinoma via regulating the Caspase-3/Bax/Bcl-2 signaling pathway# br. Acta Anat. 2020;51(2):216-8.
29. Cardoso AL, Guedes JR, Pereira de Almeida L, Pedroso de Lima MCJI. miR‐155 modulates microglia‐mediated immune response by down‐regulating SOCS‐1 and promoting cytokine and nitric oxide production. Immunol. 2012;135(1):73-88.
30. Berishaj M, Gao SP, Ahmed S, Leslie K, Al-Ahmadie H, Gerald WL, et al. STAT3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer. Breast Cancer Res. 2007;9(3):1-8.
31. Alexander WS, Hilton DJ. The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu Rev Immunol. 2004 Apr 23;22:503-29.
32. Sullivan N, Sasser A, Axel AE, Vesuna F, Raman V, Ramirez N, et al. Interleukin-6 induces an epithelial–mesenchymal transition phenotype in human breast cancer cells. Oncogene. 2009;28(33):2940-7.
33. Ahmad N, Ammar A, Storr SJ, Green AR, Rakha E, Ellis IO, Martin SG. IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients. Cancer Immunol Immunother. 2018 Apr;67(4):537-49.
34. Lippitz BE, Harris RA. Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis. Oncoimmunol. 2016 May 3;5(5):e1093722.
2. Reznikov AJEo. Hormonal impact on tumor growth and progression. Exp Oncol. 2015;37(3):162-72.
3. Moore HC, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015;372(10):923-32.
4. Li CI, Daling JR, Porter PL, Tang MTC, Malone KEJCr. Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor–Specific Subtypes of Contralateral Breast Cancer. Cancer Res. 2009;69(17):6865-70.
5. Zhu W, Qin W, Atasoy U, Sauter ERJBrn. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes. 2009;2(1):1-5.
6. Zhao C, Sun X, Li LJE. Biogenesis and function of extracellular miRNAs. ExRNA. 2019;1(1):1-9.
7. Faraoni I, Antonetti FR, Cardone J, BonmassarEJBeBA-MBoD. miR-155 gene: a typical multifunctional microRNA. BiochimBiophys Acta Gene Regul Mech. 2009;1792(6):497-505.
8. Vanni I, Alama A, Grossi F, Dal Bello MG, Coco SJDDT. Exosomes: a new horizon in lung cancer. Drug Discov Today. 2017;22(6):927-36.
9. Gillespie P, Ladame S, O'Hare DJA. Molecular methods in electrochemical microRNA detection. Anal. 2019;144(1):114-9.
10. Meseure D, DrakAlsibai K, Nicolas A, Bieche I, MorillonAJBri. Long noncoding RNAs as new architects in cancer epigenetics, prognostic biomarkers, and potential therapeutic targets. Biomed Res Int.2015;2015:320214.
11. Tomar D, Yadav AS, Kumar D, Bhadauriya G, Kundu GCJBeBA-GRM. Non-coding RNAs as potential therapeutic targets in breast cancer. BiochimBiophys Acta Gene Regul Mech.2020;1863(4):194378-9.
12. Nobili L, Ronchetti D, Taiana E, Neri AJO. Long non-coding RNAs in B-cell malignancies: a comprehensive overview. Oncotarget. 2017;8(36):60605.
13. Xia S, Feng J, Lei L, Hu J, Xia L, Wang J, et al. Comprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes. Brief Bioinform. 2017;18(6):984-92.
14. Witten LW, Cheng CJ, Slack FJJO. miR-155 drives oncogenesis by promoting and cooperating with mutations in the c-Kit oncogene. Oncogene. 2019;38(12):2151-61.
15. Jiang M, Zhang W-w, Liu P, Yu W, Liu T, Yu JJFii. Dysregulation of SOCS-mediated negative feedback of cytokine signaling in carcinogenesis and its significance in cancer treatment. Front Immunol. 2017;8:70.
16. Dudda JC, Salaun B, Ji Y, Palmer DC, Monnot GC, Merck E, et al. MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer. Immunity. 2013;38(4):742-53.
17. Yoshimura A, Ito M, Chikuma S, Akanuma T, NakatsukasaHJCSHpib. Negative regulation of cytokine signaling in immunity. Cold Spring HarbPerspect Biol. 2018;10(7):a028571.
18. Gershovich P, Karabelskii A, Ulitin A, Ivanov RJB. The role of checkpoint inhibitors and cytokines in adoptive cell-based cancer immunotherapy with genetically modified T cells. Biochem. 2019;84(7):695-710.
19. Korneev KV, Atretkhany K-SN, Drutskaya MS, Grivennikov SI, Kuprash DV, Nedospasov SAJC. TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis. Cytokine. 2017;89(12):127-35.
20. Li J, Mo H-Y, Xiong G, Zhang L, He J, Huang Z-F, et al. Tumor microenvironment macrophage inhibitory factor directs the accumulation of interleukin-17-producing tumor-infiltrating lymphocytes and predicts favorable survival in nasopharyngeal carcinoma patients. J Biol Chem. 2012;287(42):35484-95.
21. Xie G, Yao Q, Liu Y, Du S, Liu A, Guo Z, et al. IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures. Int J Oncol. 2012;40(4):1171-9.
22. Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, et al. Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PloS one. 2012;7:e47003.
23. Cortez MA, Welsh JW, Calin GA. Circulating microRNAs as noninvasive biomarkers in breast cancer. Minimal residual disease and circulating tumor cells in breast cancer: Springer. 2012;14(3):151-61.
24. Fuksiewicz M, Kowalska M, Kotowicz B, Rubach M, Chechlinska M, Pienkowski T, et al. Serum soluble tumour necrosis factor receptor type I concentrations independently predict prognosis in patients with breast cancer. Clin Chem Lab Med. 2010;48(10):1481-6.
25. Bousoik E, MontazeriAliabadiHJFio. “Do we know jack” about JAK? A closer look at JAK/STAT signaling pathway. Front Oncol. 2018;8(2):287.
26. Tanaka T, Narazaki M, KishimotoTJCSHpib. IL-6 in inflammation, immunity, and disease. Cold Spring HarbPerspect Biol. 2014;6(10):a016295.
27. Asroel EM.PengaruhPemberianMaduTerhadapPerubahan Kadar Soluble Fms-Like Tyrosine Kinase (Sflt-1), Soluble Endoglin (Seng), Vascular Endothelial Growth Factor (Vegf), Placental Growth Factor (Plgf), Tumor Necrosis Factor Alpha (Tnf-Α), Dan Interleukin 6 (Il-6) Pada Tikus Model Preeklamsia. repositori.usu.ac.id. 2020.
28. Xiao-juan MY-cD, Feng-xia LH-lCJAAS. Tumorigenic effect of interleukin-6 on mice with pancreatic carcinoma via regulating the Caspase-3/Bax/Bcl-2 signaling pathway# br. Acta Anat. 2020;51(2):216-8.
29. Cardoso AL, Guedes JR, Pereira de Almeida L, Pedroso de Lima MCJI. miR‐155 modulates microglia‐mediated immune response by down‐regulating SOCS‐1 and promoting cytokine and nitric oxide production. Immunol. 2012;135(1):73-88.
30. Berishaj M, Gao SP, Ahmed S, Leslie K, Al-Ahmadie H, Gerald WL, et al. STAT3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer. Breast Cancer Res. 2007;9(3):1-8.
31. Alexander WS, Hilton DJ. The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu Rev Immunol. 2004 Apr 23;22:503-29.
32. Sullivan N, Sasser A, Axel AE, Vesuna F, Raman V, Ramirez N, et al. Interleukin-6 induces an epithelial–mesenchymal transition phenotype in human breast cancer cells. Oncogene. 2009;28(33):2940-7.
33. Ahmad N, Ammar A, Storr SJ, Green AR, Rakha E, Ellis IO, Martin SG. IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients. Cancer Immunol Immunother. 2018 Apr;67(4):537-49.
34. Lippitz BE, Harris RA. Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis. Oncoimmunol. 2016 May 3;5(5):e1093722.
| Files | ||
| Issue | Vol 21 No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i1.8608 | |
| Keywords | ||
| Breast neoplasms IL-6 MicroRNA Suppressor of cytokine signaling | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Iranparast S, Tahmasebi-Birgani M, Motamedfar A, Amari A, Ghafourian M. Altered Expression Levels of MicroRNA-155 and SOCS-1 in Peripheral Blood Mononuclear Cells of Newly Diagnosed Breast Cancer Patients. Iran J Allergy Asthma Immunol. 2022;21(1):12-19.
