BPTF activates the MAPK pathway through coexpression with Raf1 to promote proliferation of T‑cell lymphoma

Bai,Dongyu; Zhou,Yong; Shen,Fayan; Gao,Dehong; Suo,Wenhao; Zhang,Haiping; Li,Heng

doi:10.3892/ol.2022.13344

BPTF activates the MAPK pathway through coexpression with Raf1 to promote proliferation of T‑cell lymphoma

Authors:
- Dongyu Bai
- Yong Zhou
- Fayan Shen
- Dehong Gao
- Wenhao Suo
- Haiping Zhang
- Heng Li
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Affiliations: Department of Pathology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China, Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China, Department of Pathology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China, Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China
Published online on: May 25, 2022 https://doi.org/10.3892/ol.2022.13344
Article Number: 223
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the role and biological function of bromodomain PHD finger transcription factor (BPTF) in T‑cell lymphoma. Reverse transcription‑quantitative PCR (RT‑qPCR), western blotting, immunohistochemistry and bioinformatics analysis were used to determine the expression levels of BPTF and Raf1 in T‑cell lymphoma tissues and matched adjacent normal tissues. RT‑qPCR and western blot analyses were used to examine the role of BPTF in the activation of MAPK signaling. The function of BPTF and Raf1 in T‑cell lymphoma was investigated through in vitro and in vivo assays (MTT assay, colony formation assay, flow cytometry, western blotting, tumor xenograft model and TUNEL assay) following silencing and overexpression experiments in Hut‑102 cells. The results demonstrated that BPTF and Raf1 were overexpressed in T‑cell lymphoma tissues compared with normal tissues, and high expression of BPTF or Raf1 was associated with advanced clinical stage. BPTF promoted the activation of the MAPK pathway and was coexpressed with Raf1 in T‑cell lymphoma tissues. Functional assays demonstrated that silencing of BPTF or Raf1 in Hut‑102 cells suppressed cell proliferation and induced apoptosis. Furthermore, the carcinogenic effect of BPTF was confirmed by xenograft experiments in nude mice. The present findings suggested that BPTF may function as a crucial oncogenic factor and may serve as a novel therapeutic target in T‑cell lymphoma.

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1	Evens AM, Querfeld C and Rosen ST: T-cell non-Hogdkin's lymphoma. Cancer Treat Res. 131:161–220. 2006. View Article : Google Scholar : PubMed/NCBI
2	The world health organization classification of malignant lymphomas in Japan, . Incidence of recently recognized entities. Lymphoma study group of Japanese pathologists. Pathol Int. 50:696–702. 2000. View Article : Google Scholar
3	Mugnaini EN and Ghosh N: Lymphoma. Prim Care. 43:661–675. 2016. View Article : Google Scholar : PubMed/NCBI
4	Nair R and Neelapu SS: The promise of CAR T-cell therapy in aggressive B-cell lymphoma. Best Pract Res Clin Haematol. 31:293–298. 2018. View Article : Google Scholar
5	Grimm KE and O'Malley DP: Aggressive B cell lymphomas in the 2017 revised WHO classification of tumors of hematopoietic and lymphoid tissues. Ann Diagn Pathol. 38:6–10. 2019. View Article : Google Scholar
6	Alkhatib SG and Landry JW: The nucleosome remodeling factor. FEBS Lett. 585:3197–3207. 2011. View Article : Google Scholar
7	Zhao X, Zheng F, Li Y, Hao J, Tang Z, Tian C, Yang Q, Zhu T, Diao C, Zhang C, et al: BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits. Redox Biol. 20:427–441. 2019. View Article : Google Scholar
8	Dai M, Hu S, Liu CF, Jiang L, Yu W, Li ZL, Guo W, Tang R, Dong CY, Wu TH and Deng WG: BPTF cooperates with p50 NF-κB to promote COX-2 expression and tumor cell growth in lung cancer. Am J Transl Res. 11:7398–7409. 2019.PubMed/NCBI
9	Dar AA, Majid S, Bezrookove V, Phan B, Ursu S, Nosrati M, De Semir D, Sagebiel RW, Miller JR III, Debs R, et al: BPTF transduces MITF-driven prosurvival signals in melanoma cells. Proc Natl Acad Sci USA. 113:6254–6258. 2016. View Article : Google Scholar : PubMed/NCBI
10	Richart L, Real FX and Sanchez-Arevalo Lobo VJ: c-MYC partners with BPTF in human cancer. Mol Cell Oncol. 3:e11523462016. View Article : Google Scholar
11	Peluso I, Yarla NS, Ambra R, Pastore G and Perry G: MAPK signalling pathway in cancers: Olive products as cancer preventive and therapeutic agents. Semin Cancer Biol. 56:185–195. 2019. View Article : Google Scholar
12	Zou X and Blank M: Targeting p38 MAP kinase signaling in cancer through post-translational modifications. Cancer Lett. 384:19–26. 2017. View Article : Google Scholar
13	Rezatabar S, Karimian A, Rameshknia V, Parsian H, Majidinia M, Kopi TA, Bishayee A, Sadeghinia A, Yousefi M, Monirialamdari M and Yousefi B: RAS/MAPK signaling functions in oxidative stress, DNA damage response and cancer progression. J Cell Physiol. Feb 27–2019.(Epub ahead of print). View Article : Google Scholar
14	Davis JA: Mouse and rat anesthesia and analgesia. Curr Protoc Neurosci. Jan 1–2008.(Epub ahead of print). View Article : Google Scholar
15	Adams S and Pacharinsak C: Mouse anesthesia and analgesia. Curr Protoc Mouse Biol. 5:51–63. 2015. View Article : Google Scholar
16	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar
17	Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, et al: STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47:D607–D613. 2019. View Article : Google Scholar : PubMed/NCBI
18	Jiang M, Bennani NN and Feldman AL: Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms. Expert Rev Hematol. 10:239–249. 2017. View Article : Google Scholar
19	Jaffe ES: Diagnosis and classification of lymphoma: Impact of technical advances. Semin Hematol. 56:30–36. 2019. View Article : Google Scholar
20	Yu L, Li L, Medeiros LJ and Young KH: NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms. Blood Rev. 31:77–92. 2017. View Article : Google Scholar : PubMed/NCBI
21	Yang W, Wang Y, Yu Z, Li Z, An G, Liu W, Lv R, Ma L, Yi S and Qiu L: SOX11 regulates the pro-apoptosis signal pathway and predicts a favorable prognosis of mantle cell lymphoma. Int J Hematol. 106:212–220. 2017. View Article : Google Scholar
22	Miller AL, Geng C, Golovko G, Sharma M, Schwartz JR, Yan J, Sowers L, Widger WR, Fofanov Y, Vedeckis WV and Thompson EB: Epigenetic alteration by DNA-demethylating treatment restores apoptotic response to glucocorticoids in dexamethasone-resistant human malignant lymphoid cells. Cancer Cell Int. 14:352014. View Article : Google Scholar
23	Sun RF, Yu QQ and Young KH: Critically dysregulated signaling pathways and clinical utility of the pathway biomarkers in lymphoid malignancies. Chronic Dis Transl Med. 4:29–44. 2018.PubMed/NCBI
24	Gong YC, Liu DC, Li XP and Dai SP: BPTF biomarker correlates with poor survival in human NSCLC. Eur Rev Med Pharmacol Sci. 21:102–107. 2017.
25	Nakagawa H and Fujita M: Whole genome sequencing analysis for cancer genomics and precision medicine. Cancer Sci. 109:513–522. 2018. View Article : Google Scholar
26	Pauli C, Hopkins BD, Prandi D, Shaw R, Fedrizzi T, Sboner A, Sailer V, Augello M, Puca L, Rosati R, et al: Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov. 7:462–477. 2017. View Article : Google Scholar : PubMed/NCBI