PROLIFERATION AND APOPTOSIS OF B-CELL LYMPHOMA CELLS UNDER TARGETED REGULATION OF FOXO3 BY miR-155 miR-155, FOXO3, B-cell lymphoma, proliferation, apoptosis, clinical characteristics
Main Article Content
Keywords
miR-155, FOXO3, B-cell lymphoma, proliferation, apoptosis, clinical characteristics
Abstract
This study aimed to explore the proliferation and apoptosis of B-cell lymphoma cells under targeted regulation of FOXO3 by miR-155. We analyzed the differences between B-cell lymphoma cells and B lymphocytes in expressions of miR-155 and FOXO3, explored the effects of miR-155 on proliferation and apoptosis of B-cell lymphoma cells, and relevant mechanisms, and also analyzed the relationship between expressions of miR-155 and FOXO3 in 42 patients with diffuse large B-cell lymphoma (DLBCL) and clinical characteristics of them. B-cell lymphoma cells showed a higher expression of miR-155 and a low expression of FOXO3 than B lymphocytes (both P<0.05). B-cell lymphoma cells transfected with miR-155-inhibitor showed significantly decreased expression of miR-155, significantly weakened cell proliferation ability and increased cell apoptosis rate (all P<0.05), and they also showed up-regulated expression of FOXO3 (P<0.05). Dual luciferase reporter assay revealed that there were targeted binding sites between miR-155 and FOXO3. Compared with B-cell lymphoma cells transfected with miR-155-inhibitor alone, those with co-transfection showed lower expression of FOXO3, higher proliferation and lower cell apoptosis rate (all P<0.05). The expression of miR-155 in DLBCL tissues was higher than that in tumor-adjacent tissues (P<0.05), and the expressions of miR-155 and FOXO3 were closely related to the international prognostic index (IPI) and the 5-year prognosis and survival of the patients (P<0.05). miR-155 can promote the proliferation of B-cell lymphoma cells and suppress apoptosis of them by targeted inhibiting FOXO3, and both over-expression of miR-155 and low expression of FOXO3 are related to poor prognosis of DLBCL patients.
Downloads
Abstract 289
PDF Downloads 19
HTML Downloads 74
References
2. Swerdlow SH: WHO classification of tumours of haematopoietic and lymphoid tissues. WHO classification of tumours 22008: 439, 2008.
3. Horwitz SM, Zelenetz AD, Gordon LI, Wierda WG, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Byrd JC, Fayad LE, et al: NCCN guidelines insights:non-Hodgkin's lymphomas, version 3.2016. J Natl Compr Canc Netw 14: 1067-1079, 2016.
4. Lenz G, Wright GW, Emre NC, Kohlhammer H, Dave SS, Davis RE, Carty S, Lam LT, Shaffer AL, Xiao W, et al: Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A 105: 13520-13525, 2008.
5. Gonçalves OSL, Wheeler G, Dalmay T, et al: Detection of miRNA cancer biomarkers using light activated Molecular Beacons. Rsc Advances 9: 12766-12783, 2019.
6. Mullany LE, Herrick JS, Sakoda LC, Samowitz W, Stevens JR, Wolff RK and Slattery ML: miRNA involvement in cell cycle regulation in colorectal cancer cases. Genes Cancer 9: 53, 2018.
7. Zhang J, Wei B, Hu H, Liu F, Tu Y, Zhao M and Wu D: Preliminary study on decreasing the expression of FOXP3 with miR-155 to inhibit diffuse large B-cell lymphoma. Oncol Lett 14: 1711-1718, 2017.
8. Huang X, Shen Y, Liu M, Bi C, Jiang C, Iqbal J, McKeithan TW, Chan WC, Ding SJ, Fu K: Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma. Am J Pathol 181: 26-33, 2012.
9. Coomans de Brachène A and Demoulin JB: FOXO transcription factors in cancer development and therapy. Cell Mol Life Sci 73: 1159-1172, 2016.
10. Obrador-Hevia A, Serra-Sitjar M, Rodríguez J, Villalonga P and Fernández de Mattos S: The tumour suppressor FOXO3 is a key regulator of mantle cell lymphoma proliferation and survival. Br J Haematol 156: 334-345, 2012.
11. He B, Yan F and Wu C: Overexpressed miR-195 attenuated immune escape of diffuse large B-cell lymphoma by targeting PD-L1. Biomed Pharmacother 98: 95-101, 2018.
12. Huang J, Jiao J, Xu W, Zhao H, Zhang C, Shi Y and Xiao Z: MiR-155 is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO3. Mol Med Rep 12: 7102-7108, 2015.
13. 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.
14. Van Roosbroeck K, Fanini F, Setoyama T, Ivan C, Rodriguez-Aguayo C, Fuentes-Mattei E, Xiao L, Vannini I, Redis RS, D'Abundo L, et al: Combining anti-miR-155 with chemotherapy for the treatment of lung cancers. Clin Cancer Res 23: 2891-2904, 2017.
15. Zargar S, Tomar V, Shyamsundar V, Vijayalakshmi R, Somasundaram K and Karunagaran D: A feedback loop between microRNA 155 (miR-155), programmed cell death 4, and activation protein 1 modulates the expression of miR-155 and tumorigenesis in tongue cancer. Mol?Cell?Biol 39: e00410-18, 2019.
16. Yao S, Fan LY and Lam EW: The FOXO3-FOXM1 axis:A key cancer drug target and a modulator of cancer drug resistance[C]//Seminars in cancer biology. Semin Cancer Biol 50: 77-89, 2018.
17. Kumazoe M, Takai M, Bae J, Hiroi S, Huang Y, Takamatsu K, Won Y, Yamashita M, Hidaka S, Yamashita S, et al: FOXO3 is essential for CD44 expression in pancreatic cancer cells. Oncogene 36: 2643, 2017.
18. Slezak-Prochazka I, Kluiver J, de Jong D, Smigielska-Czepiel K, Kortman G, Winkle M, Rutgers B, Koerts J, Visser L, Diepstra A, et al: Inhibition of the miR-155 target NIAM phenocopies the growth promoting effect of miR-155 in B-cell lymphoma. Oncotarget 7: 2391, 2016.
19. Ushmorov A and Wirth T: FOXO in B-cell lymphopoiesis and B cell neoplasia[C]//Seminars in cancer biology. Semin Cancer Biol 50: 132-141, 2018.
20. Zhang L, Cai M, Gong Z, Zhang B, Li Y, Guan L, Hou X, Li Q, Liu G, Xue Z, et al: Geminin facilitates FoxO3 deacetylation to promote breast cancer cell metastasis. J Clin Invest 127: 2159-2175, 2017.
21. Kumazoe M, Takai M, Hiroi S, Takeuchi C, Kadomatsu M, Nojiri T, Onda H, Bae J, Huang Y, Takamats u K, et al: The FOXO3/PGC-1? signaling axis is essential for cancer stem cell properties of pancreatic ductal adenocarcinoma. J Biol Chem 292: 10813-10823, 2017.
22. Kim S, Lee E, Jung J, Lee JW, Kim HJ, Kim J, Yoo HJ, Lee HJ, Chae SY, Jeon SM, et al: microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer. Oncogene 37: 2982, 2018.
23. Zhang Y, Zhao H and Zhang L: Identification of the tumor suppressive function of circular RNA FOXO3 in non small cell lung cancer through sponging miR 155. Mol Med Rep 17: 7692-7700, 2018.
24. Ji H, Tian D, Zhang B, Zhang Y, Yan D and Wu S: Overexpression of miR 155 in clear cell renal cell carcinoma and its oncogenic effect through targeting FOXO3a. Exp Ther Med 13: 2286-2292, 2017.
25. Andor N, Simonds EF, Czerwinski DK, Chen J, Grimes SM, Wood-Bouwens C, Zheng GXY, Kubit MA, Greer S, Weiss WA, et al: Single-cell RNA-Seq of follicular lymphoma reveals malignant B-cell types and coexpression of T-cell immune checkpoints. Blood 133: 1119-1129, 2019.
26. Togher S, Larange A, Schoenberger SP and Feau S:FoxO3 is a negative regulator of primary CD8+ T?cell expansion but not of memory formation. Immunol Cell Biol 93: 120-125, 2015.
27. Ottens K, Hinman RM, Barrios E, Skaug?B, Davis LS, Li QZ, Castrillon DH and Satterthwaite AB: Foxo3 Promotes Apoptosis of B Cell Receptor–Stimulated Immature B Cells, Thus Limiting the Window for Receptor Editing. J Immunol 201: 940-949, 2018.
28. Due H, Svendsen P, Bødker JS, Schmitz A, Bøgsted M, Johnsen HE, El-Galaly TC, Roug AS and Dybkær K: miR-155 as a Biomarker in B-Cell Malignancies. Biomed Res Int 2016: 1-14, 2016.
29. Ahmadvand M, Eskandari M, Pashaiefar H, Yaghmaie M, Manoochehrabadi S, Khakpour G, Sheikhsaran F and Montazer Zohour M: Over expression of circulating miR-155 predicts prognosis in diffuse large B-cell lymphoma. Leuk Res 70: 45-48, 2018.
30. Khoshinani HM, Afshar S, Pashaki AS, Mahdavinezhad A, Nikzad S, Najafi R, Amini R, Gholami MH, Khoshghadam A and Saidijam M: Involvement of miR-155/FOXO3a and miR-222/PTEN in acquired radioresistance of colorectal cancer cell line. Jpn J Radiol 35: 664-672, 2017.
Article Sidebar
Article Details
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers. Authors will grant copyright of their articles to the Institute of Hematology, Catholic University, Rome . No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.