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miR-370 增强 TMZ 对原发性中枢神经系统淋巴瘤的反应,依赖于 MGMT 状态。

miR-370 Sensitizes TMZ Response Dependent of MGMT Status in Primary Central Nervous System Lymphoma.

机构信息

Department of Neurosurgery, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, 310016, People's Republic of China.

Department of Neurosurgery, Hangzhou Xiasha Hospital, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, 310016, People's Republic of China.

出版信息

Pathol Oncol Res. 2020 Apr;26(2):707-714. doi: 10.1007/s12253-019-00605-4. Epub 2019 Feb 2.

DOI:10.1007/s12253-019-00605-4
PMID:30712191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7242252/
Abstract

Primary central nervous system lymphoma (PCNSL) is an aggressive and rare subtype of non-Hodgkin lymphoma, arising exclusively in the CNS with a poor prognosis. Previous evidence has proved that MGMT was a promising target involving in TMZ resistance of PCNSL. Our study described a new miR-370-mediated mechanism of MGMT regulation in PCNSL. We first showed that miR-370 was downregulated in PCNSL tissues, while MGMT was inversely overexpressed. It was also observed that miR-370 suppressed the expression of MGMT. Additionally, upregulation of miR-370 significantly increased TMZ sensitivity dependent of MGMT, thus suppressed Raji cell proliferation and induced apoptosis in vitro. In conclusion, these results suggest that miR-370 is a potential target in PCNSL treatment.

摘要

原发性中枢神经系统淋巴瘤(PCNSL)是一种侵袭性和罕见的非霍奇金淋巴瘤亚型,仅在中枢神经系统中发生,预后不良。先前的证据已经证明,MGMT 是一个有前途的靶点,涉及 PCNSL 对 TMZ 的耐药性。我们的研究描述了 PCNSL 中 MGMT 调节的一种新的 miR-370 介导的机制。我们首先表明,miR-370 在 PCNSL 组织中下调,而 MGMT 则相反过表达。还观察到 miR-370 抑制 MGMT 的表达。此外,miR-370 的上调显著增加了 TMZ 敏感性,依赖于 MGMT,从而抑制 Raji 细胞的增殖并在体外诱导细胞凋亡。总之,这些结果表明 miR-370 是 PCNSL 治疗的一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/77d94862574a/12253_2019_605_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/ffa72d792df1/12253_2019_605_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/71248c5119c5/12253_2019_605_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/b8c2075f0c8e/12253_2019_605_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/6c13991c1570/12253_2019_605_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/77d94862574a/12253_2019_605_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/ffa72d792df1/12253_2019_605_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/71248c5119c5/12253_2019_605_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/b8c2075f0c8e/12253_2019_605_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/6c13991c1570/12253_2019_605_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fea/7242252/77d94862574a/12253_2019_605_Fig5_HTML.jpg

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