PRMT5 promotes colorectal cancer growth by interaction with MCM7.
PRMT5 promotes colorectal cancer growth by interaction with MCM7.
复制标题
DOI：
10.1111/jcmm.16436
复制
发表时间：
2021-04
影响因子：
5.3
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Li X;Wang X;Zhao J;Wang J;Wu J
蛋白质精氨酸甲基转移酶5（PRMT 5）是一种甲基转移酶，可以催化组蛋白和非组蛋白的精氨酸甲基化。越来越多的证据表明PRMT 5促进癌症的发展和进展。然而，其在结直肠癌（CRC）中的功能知之甚少。在这项研究中，我们揭示了PRMT 5在CRC中的致癌作用。我们发现PRMT 5在体外和体内促进CRC细胞增殖、迁移和侵袭。我们确定了微小染色体维持-7（MCM 7）作为PRMT 5的直接结合伴侣。免疫共沉淀（co-IP）试验表明，PRMT 5与MCM 7发生物理相互作用，直接结合结构域位于MCM 7的残基1 - 248之间。此外，我们对99例CRC组织和77例邻近非癌组织的分析结果表明，CRC组织中PRMT 5和MCM 7的表达水平显著高于对照组织，这一点通过使用TCGA和GEO数据集的生物信息学分析得到了进一步证实。我们还发现MCM 7在体外促进CRC细胞的增殖、迁移和侵袭。此外，我们观察到PRMT 5表达增加预测CRC患者和肿瘤大小≤5 cm的患者亚组的患者生存率不利。这些数据表明PRMT 5和MCM 7可能是治疗CRC的新的潜在靶点。
Protein arginine methyltransferase 5 (PRMT5) is a type of methyltransferase enzyme that can catalyse arginine methylation of histones and non‐histone proteins. Accumulating evidence indicates that PRMT5 promotes cancer development and progression. However, its function in colorectal cancer (CRC) is poorly understood. In this study, we revealed the oncogenic roles of PRMT5 in CRC. We found that PRMT5 promoted CRC cell proliferation, migration and invasion in vitro and in vivo. We identified minichromosome maintenance‐7 (MCM7) as the direct PRMT5‐binding partner. A co‐immunoprecipitation (co‐IP) assay indicated that PRMT5 physically interacted with MCM7 and that the direct binding domain was located between residues 1‐248 in MCM7. In addition, our results from analysis of 99 CRC tissues and 77 adjacent non‐cancerous tissues indicated that the PRMT5 and MCM7 expression levels were significantly higher in CRC tissues than in control tissues, which was further confirmed by bioinformatic analysis using TCGA and GEO datasets. We also found that MCM7 promoted CRC cell proliferation, migration and invasion in vitro. Furthermore, we observed that increased PRMT5 expression predicted unfavourable patient survival in CRC patients and in the subgroup of patients with a tumour size of ≤5 cm. These data suggested that PRMT5 and MCM7 might be novel potential targets for the treatment of CRC.
登录
查看更多内容
DOI：
10.1073/pnas.0911500106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Evrin, Cecile;Clarke, Pippa;Speck, Christian
通讯作者：
Speck, Christian
影响因子：
8
作者：
Pillaire, M-J;Selves, J.;Cazaux, C.
通讯作者：
Cazaux, C.
影响因子：
21.3
作者：
Jansson, Martin;Durant, Stephen T.;La Thangue, Nicholas B.
通讯作者：
La Thangue, Nicholas B.
影响因子：
11.5
作者：
Kemper, Kristel;Versloot, Miranda;Medema, Jan Paul
通讯作者：
Medema, Jan Paul
影响因子：
5.2
作者：
Nishihara, Keisuke;Shomort, Kohei;Ito, Hisao
通讯作者：
Ito, Hisao