Integrative genomic analyses of the RNA-binding protein, RNPC1, and its potential role in cancer prediction
Integrative genomic analyses of the RNA-binding protein, RNPC1, and its potential role in cancer prediction
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RNA 结合蛋白 RNPC1 的整合基因组分析及其在癌症预测中的潜在作用。
DOI：
10.3892/ijmm.2015.2237
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发表时间：
2015-08-01
影响因子：
5.4
通讯作者：
Ding, Qiang
中科院分区：
文献类型：
--
作者：
Ding, Zhiming;Yang, Hai-Wei;Ding, Qiang
RNA结合基序蛋白38（RBM 38，也称为RNPC 1）在调节从细胞增殖和细胞周期停滞到细胞肌源性分化的广泛生物过程中起关键作用。它最初被认为是一种致癌基因，经常被发现在前列腺癌、卵巢癌和结肠直肠癌、慢性淋巴细胞白血病、结肠癌、食道癌、狗淋巴瘤和乳腺癌中扩增。在本研究中，完整的RNPC 1基因在许多脊椎动物的基因组中被确定，表明RNPC 1存在于所有类型的脊椎动物，包括鱼类，两栖动物，鸟类和哺乳动物。在不同的基因组中，该基因具有相似的4外显子/3内含子结构，并且所有的遗传位点都是同线保守的。系统发育树显示，RNPC 1基因在哺乳动物、鸟类、爬行动物和硬骨鱼类中形成了一个种属特异的聚类。在人RNPC 1基因中共鉴定出34个功能相关的单核苷酸多态性（SNP），包括14个引起错义突变的SNP、8个外显子剪接增强子SNP和12个引起无义突变的SNP。RNPC 1在膀胱癌、血癌、脑癌、乳腺癌、结直肠癌、眼癌、头颈癌、肺癌、卵巢癌、皮肤癌和软组织癌中均有表达。在94项测试中的14项中，观察到RNPC 1基因表达与癌症预后之间的关联。我们发现RNPC 1的表达与预后之间的关联在不同类型的癌症中是不同的，甚至在来自不同数据库的相同类型的癌症中也是不同的。这表明RNPC 1在这些肿瘤中的功能可能是多维的。性别决定区Y（SRY）-盒5（Sox 5）、矮小相关转录因子3（RUNX 3）、CCAAT置换蛋白1（CUTL 1）、v-rel禽网状内皮组织增生症病毒癌基因同源物（Rel）A，过氧化物酶体增殖物激活受体γ亚型2（PPARγ2）和转录激活因子6（ATF 6）的调节转录因子结合位点被确定在上游RNPC 1基因的启动子区，因此可能参与RNPC 1在肿瘤中的作用。
The RNA binding motif protein 38 (RBM38, also known as RNPC1) plays a pivotal role in regulating a wide range of biological processes, from cell proliferation and cell cycle arrest to cell myogenic differentiation. It was originally recognized as an oncogene, and was frequently found to be amplified in prostate, ovarian and colorectal cancer, chronic lymphocytic leukemia, colon carcinoma, esophageal cancer, dog lymphomas and breast cancer. In the present study, the complete RNPC1 gene was identified in a number of vertebrate genomes, suggesting that RNPC1 exists in all types of vertebrates, including fish, amphibians, birds and mammals. In the different genomes, the gene had a similar 4 exon/3 intron organization, and all the genetic loci were syntenically conserved. The phylogenetic tree demonstrated that the RNPC1 gene from the mammalian, bird, reptile and teleost lineage formed a species-specific cluster. A total of 34 functionally relevant single nucleotide polymorphisms (SNPs), including 14 SNPs causing missense mutations, 8 exonic splicing enhancer SNPs and 12 SNPs causing nonsense mutations, were identified in the human RNPC1 gene. RNPC1 was found to be expressed in bladder, blood, brain, breast, colorectal, eye, head and neck, lung, ovarian, skin and soft tissue cancer. In 14 of the 94 tests, an association between RNPC1 gene expression and cancer prognosis was observed. We found that the association between the expression of RNPC1 and prognosis varied in different types of cancer, and even in the same type of cancer from the different databases used. This suggests that the function of RNPC1 in these tumors may be multidimensional. The sex determining region Y (SRY)-box 5 (Sox5), runt-related transcription factor 3 (RUNX3), CCAAT displacement protein 1 (CUTL1), v-rel avian reticuloendotheliosis viral oncogene homolog (Rel)A, peroxisome proliferator-activated receptor γ isoform 2 (PPARγ2) and activating transcription factor 6 (ATF6) regulatory transcription factor binding sites were identified in the upstream (promoter) region of the RNPC1 gene, and may thus be involved in the effects of RNPC1 in tumors.