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BPTF通过与Raf1共表达激活丝裂原活化蛋白激酶(MAPK)信号通路,以促进T细胞淋巴瘤的增殖。

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

作者信息

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

机构信息

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.

出版信息

Oncol Lett. 2022 May 25;24(1):223. doi: 10.3892/ol.2022.13344. eCollection 2022 Jul.

DOI:10.3892/ol.2022.13344
PMID:35720479
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9185150/
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 and 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.

摘要

本研究旨在探讨溴结构域PHD指转录因子(BPTF)在T细胞淋巴瘤中的作用及生物学功能。采用逆转录定量PCR(RT-qPCR)、蛋白质印迹法、免疫组织化学和生物信息学分析来测定T细胞淋巴瘤组织及配对的癌旁正常组织中BPTF和Raf1的表达水平。运用RT-qPCR和蛋白质印迹分析检测BPTF在丝裂原活化蛋白激酶(MAPK)信号激活中的作用。在Hut-102细胞中进行沉默和过表达实验后,通过MTT法、集落形成实验、流式细胞术、蛋白质印迹法、肿瘤异种移植模型和TUNEL实验研究BPTF和Raf1在T细胞淋巴瘤中的功能。结果表明,与正常组织相比,BPTF和Raf1在T细胞淋巴瘤组织中过表达,且BPTF或Raf1的高表达与临床晚期相关。BPTF促进MAPK通路的激活,且在T细胞淋巴瘤组织中与Raf1共表达。功能实验表明,在Hut-102细胞中沉默BPTF或Raf1可抑制细胞增殖并诱导凋亡。此外,裸鼠异种移植实验证实了BPTF的致癌作用。本研究结果提示,BPTF可能作为关键致癌因子发挥作用,并且可能成为T细胞淋巴瘤的新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/957ddf0c7fec/ol-24-01-13344-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/d2578ec74539/ol-24-01-13344-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/49757c646c5e/ol-24-01-13344-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/aa15e8110018/ol-24-01-13344-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/a97251a408ee/ol-24-01-13344-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/957ddf0c7fec/ol-24-01-13344-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/d2578ec74539/ol-24-01-13344-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/49757c646c5e/ol-24-01-13344-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/aa15e8110018/ol-24-01-13344-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/a97251a408ee/ol-24-01-13344-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/9185150/957ddf0c7fec/ol-24-01-13344-g04.jpg

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