Associations of \(\textit{OTUBAIN-1, STAT, SHP}\) and \(\textit{NF-KB2}\) expression with clinical features in Non-Hodgkin’s lymphoma patients

Do Thi Trang, Nguyen Trong Ha, Nguyen Thi Xuan
Author affiliations

Authors

  • Do Thi Trang 103 Hospital, Vietnam Military Medical University, 261 Phung Hung, Ha Dong, Ha Noi, Vietnam
  • Nguyen Trong Ha Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Ha Noi, Vietnam; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Ha Noi, Vietnam
  • Nguyen Thi Xuan Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Ha Noi, Vietnam https://orcid.org/0000-0003-3494-5136

DOI:

https://doi.org/10.15625/2615-9023/19064

Keywords:

NF-kB2, Otubain-1, non- Hodgkin’s lymphoma and STAT5.

Abstract

Non-Hodgkin's lymphoma (NHL) is a group of lymphoproliferative disorders characterized by the abnormal proliferation and accumulation of lymphocytes in the lymphatic system. An ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (Otubain-1) is a deubiquitinating enzyme that cleaves ubiquitin or ubiquitin-like molecules and is expressed in various human tissues. The pathogenesis of NHL is associated with activations of the nuclear transcription factor (NF-κB) and signal transducer and activator of transcription proteins (JAK/STAT) signaling pathways. In this study, all the expressions of Otubain-1, NF-κB2, SHPs and STATs genes, the concentrations of cytokines IL-1β, IL-6 and TNF-α and clinical features in NHL patients were examined. To the end, gene expression levels of 82 NHL patients and 56 healthy individuals were determined by quantitative real time RT-PCR and secretion of cytokines by ELISA. As a result, concentrations of IL-6 and TNF-α in the patient group were found higher than in the healthy individuals and patients with higher LDH concentrations in the clinical cutoff, 280 U/L showed increased concentrations of AST, ALT and GGT than those with normal LDH concentrations. Interestingly, NHL patients with high Otubain-1 expression had significant elevations of GGT and ferritin concentrations as well as STAT-5 expression compared to those with low Otubain-1 expression. In conclusion, the present study indicates that up-regulation of Otubain-1 led to activation of STAT5 in lymphoma cells and liver dysfunction and metabolic syndrome in NHL patients.

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References

Chen J. L., Chu P. Y., Huang C. T., Huang T. T., Wang W. L., Lee Y. H., Chang Y. Y., Dai M. S., Shiau C. W., Liu C. Y., 2022. Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma. Mol Med, 28: 93.

Chen T., Ren Y., Liu Y., Long Y., Zhang X., Yu H., Xu J., Yu T., Tian H., 2010. Serum gamma-glutamyl transferase, ferritin and the risk of type 2 diabetes in women from a Chinese minority. Diabetes Res Clin Pract, 90: 352–7.

Chim C. S., Fung T. K., Cheung W. C., Liang R., Kwong Y. L., 2004. SOCS1 and SHP1 hypermethylation in multiple myeloma: implications for epigenetic activation of the Jak/STAT pathway. Blood, 103: 4630–5.

D'Mello K. P., Zhao L., Kaser E. C., Zhu Z., Xiao H., Wakefield M. R., Bai Q., Fang Y., 2021. The role of interleukins and the widely studied TNF-α in non-Hodgkin's lymphoma. Medical oncology (Northwood, London, England), 38: 56.

Dong Q., Siminovitch K. A., Fialkow L., Fukushima T., Downey G. P., 1999. Negative regulation of myeloid cell proliferation and function by the SH2 domain-containing tyrosine phosphatase-1. J Immunol, 162: 3220–30.

Dumontet C., Drai J., Bienvenu J., Berard E. N., Thieblemont C., Bouafia F., Bayle F., Moullet I., Salles G., Coiffier B., 1999. Profiles and prognostic values of LDH isoenzymes in patients with non-Hodgkin's lymphoma. Leukemia, 13: 811–7.

Edlefsen K. L., Martínez-Maza O., Madeleine M. M., Magpantay L., Mirick D. K., Kopecky K. J., LaCroix A. Z., De Roos A. J., 2014. Cytokines in serum in relation to future non-Hodgkin lymphoma risk: evidence for associations by histologic subtype. International journal of cancer, 135: 913–22.

Hoang N. H., Huyen N. T., Trang D. T., Canh N. X., Mao C. V., Sopjani M., Vuong N. B., Xuan N. T., 2022. Effects of Vinblastine and Vincristine on the function of chronic myeloid leukemic cells through expression of A20 and CYLD. Cell Mol Biol (Noisy-le-grand), 68: 47–53.

Hoermann G., Greiner G., Valent P., 2015. Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms. Mediators Inflamm, 2015: 869242.

Isshiki Y., Melnick A., 2021. Epigenetic Mechanisms of Therapy Resistance in Diffuse Large B Cell Lymphoma (DLBCL). Curr Cancer Drug Targets, 21: 274–82.

Karunarathna U., Kongsema M., Zona S., Gong C., Cabrera E., Gomes A.R., Man E.P.S., Khongkow P., Tsang J.W.H., Khoo U.S., Medema R.H., Freire R., Lam E.W.F., 2016. OTUB1 inhibits the ubiquitination and degradation of FOXM1 in breast cancer and epirubicin resistance. Oncogene, 35: 1433–44.

Lazzarino M., Orlandi E., Klersy C., Astori C., Brusamolino E., Corso A., Bellio L., Gargantini L., Morra E., Bernasconi C., 1998. Serum CA 125 is of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma: correlation with tumor parameters and disease activity. Cancer, 82: 576–82.

Li Y., Yang J.Y., Xie X., Jie Z., Zhang L., Shi J., Lin D., Gu M., Zhou X., Li H.S., Watowich S.S., Jain A., Yun Jung S., Qin J., Cheng X., Sun S.C., 2019. Preventing abnormal NF-κB activation and autoimmunity by Otub1-mediated p100 stabilization. Cell research, 29: 474–85.

Lin J. T., Lineberry N. B., Kattah M. G., Su L. L., Utz P. J., Fathman C. G., Wu L., 2009. Naive CD4 t cell proliferation is controlled by mammalian target of rapamycin regulation of GRAIL expression. J Immunol, 182: 5919–28.

Livak K. J., Schmittgen T. D., 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25: 402–8.

Lorenz U., 2009 SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunol Rev, 228: 342–59.

Mafra A., Laversanne M., Gospodarowicz M., Klinger P., De Paula Silva N., Pineros M., Steliarova-Foucher E., Bray F., Znaor A., 2022. Global patterns of non-Hodgkin lymphoma in 2020. Int J Cancer, 151: 1474–81.

Maroun C. R., Naujokas M. A., Holgado-Madruga M., Wong A. J., Park M., 2000. The tyrosine phosphatase SHP-2 is required for sustained activation of extracellular signal-regulated kinase and epithelial morphogenesis downstream from the met receptor tyrosine kinase. Mol Cell Biol, 20: 8513–25.

O'Sullivan J., Mead A. J., 2019. Heterogeneity in myeloproliferative neoplasms: Causes and consequences. Adv Biol Regul, 71: 55–68.

Oka T., Ouchida M., Koyama M., Ogama Y., Takada S., Nakatani Y., Tanaka T., Yoshino T., Hayashi K., Ohara N., Kondo E., Takahashi K., Tsuchiyama J., Tanimoto M., Shimizu K., Akagi T., 2002. Gene silencing of the tyrosine phosphatase SHP1 gene by aberrant methylation in leukemias/lymphomas. Cancer Res, 62: 6390–4.

Ramis-Zaldivar J. E., Gonzalez-Farre B., Nicolae A., Pack S., Clot G., Nadeu F., Mottok A., Horn H., Song J. Y., Fu K., Wright G., Gascoyne R.D., Chan W. C., Scott D.W., Feldman A.L., Valera A., Enjuanes A., Braziel R.M., Smeland E. B., Staudt L.M., Rosenwald A., Rimsza L. M., Ott G., Jaffe E.S., Salaverria I., Campo E., 2021. MAPK and JAK-STAT pathways dysregulation in plasmablastic lymphoma. Haematologica, 106: 2682–93.

Rogers B. B., 2006. Overview of non-Hodgkin's lymphoma. Semin Oncol Nurs, 22: 67–72.

Saldana M., VanderVorst K., Berg A. L., Lee H., Carraway K. L., 2019. Otubain 1: a non-canonical deubiquitinase with an emerging role in cancer. Endocrine-related cancer, 26: R1–R14.

Savli H., Akkoyunlu R. U., Cine N., Gluzman D. F., Zavelevich M. P., Sklyarenko L. M., Koval S. V., Sunnetci D., 2016. Deregulated Levels of the NF-kappaB1, NF-kappaB2, and Rel Genes in Ukrainian Patients with Leukemia and Lymphoma in the Post-Chernobyl Period. Turk J Haematol, 33: 8–14.

Swerdlow S. H., Campo E., Pileri S. A., Harris N. L., Stein H., Siebert R., Advani R., Ghielmini M., Salles G. A., Zelenetz A. D., Jaffe E. S., 2016. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood, 127: 2375–90.

Tajan M., de Rocca Serra A., Valet P., Edouard T., Yart A., 2015. SHP2 sails from physiology to pathology. Eur J Med Genet, 58: 509–25.

Voena C., Conte C., Ambrogio C., Boeri Erba E., Boccalatte F., Mohammed S., Jensen O.N., Palestro G., Inghirami G., Chiarle R., 2007. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. Cancer Res, 67: 4278–86.

Wang X. L., Wang X. L., He S., Zhai H. L., 2015. Association of beta2-microglobulin with the prognosis of non-Hodgkin's lymphoma: a meta analysis. Int J Clin Exp Med, 8: 3992–9.

Weng W., Zhang Q., Xu M., Wu Y., Zhang M., Shen C., Chen X., Wang Y., Sheng W., 2016. OTUB1 promotes tumor invasion and predicts a poor prognosis in gastric adenocarcinoma. American journal of translational research, 8: 2234–44.

Witkiewicz A., Raghunath P., Wasik A., Junkins-Hopkins J.M., Jones D., Zhang Q., Odum N., Wasik M. A., 2007. Loss of SHP-1 tyrosine phosphatase expression correlates with the advanced stages of cutaneous T-cell lymphoma. Hum Pathol, 38: 462–7.

Xuan N. T., Trung D. M., Minh N. N., Nghia V. X., Giang N. V., Canh N. X., Toan N. L., Cam T. D., Nga N. T., Tien T. V., Hoang N. H., 2019. Regulation of p38MAPK-mediated dendritic cell functions by the deubiquitylase otubain 1. HLA, 93: 462–70.

Xuan N. T., Wang X., Nishanth G., Waisman A., Borucki K., Isermann B., Naumann M., Deckert M., Schluter D., 2015. A20 expression in dendritic cells protects mice from LPS-induced mortality. Eur J Immunol, 45: 818–28.

Zhang Y., Tong L., Chen S., Wu W., Wang L., 2018. Analysis of NFKB2‑mediated regulation of mechanisms underlying the development of Hodgkin's lymphoma. Molecular medicine reports, 17: 8129–36.

Zhong H., Chen J., Cheng S., Chen S., Shen R., Shi Q., Xu P., Huang H., Zhang M., Wang L., Wu D., Zhao W., 2019. Prognostic nomogram incorporating inflammatory cytokines for overall survival in patients with aggressive non-Hodgkin’s lymphoma. EBioMedicine, 41: 167–74.

Zhou Y., Wu J., Fu X., Du W., Zhou L., Meng X., Yu H., Lin J., Ye W., Liu J., Peng H., Liu R.-y., Pan C., Huang W., 2014. OTUB1 promotes metastasis and serves as a marker of poor prognosis in colorectal cancer. Molecular Cancer, 13: 258.

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Published

29-03-2024

How to Cite

Do Thi, T., Nguyen Trong, H., & Nguyen, X. T. (2024). Associations of \(\textit{OTUBAIN-1, STAT, SHP}\) and \(\textit{NF-KB2}\) expression with clinical features in Non-Hodgkin’s lymphoma patients. Academia Journal of Biology, 46(1), 69–78. https://doi.org/10.15625/2615-9023/19064

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