Integrative genomic analyses of the RNA-binding protein, RNPC1, and its potential role in cancer prediction

Abstract

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.

Molecular cloning, expression, IgE binding activities and in silico epitope prediction of Per a 9 allergens of the American cockroach

“…The phylogenetic tree was obtained by using the maximum-likelihood (ML) method on the basis of the JTT amino acid sequence distance implemented in MEGA 5.1, and the reliability was evaluated by the bootstrap method with 1,000 replications (24–32). …”

In silico epitope prediction, expression and functional analysis of Per a 10 allergen from the American cockroach

“…The phylogenetic tree of Per a 10 and its homolog was obtained by the maximum-likelihood (ML) method on the basis of the JTT amino acid sequence distance implemented in MEGA 5.1, the reliability was evaluated by the bootstrap method with 1,000 replications (28–32). …”

The expression of RNA-binding protein RBM38 decreased in renal cell carcinoma and represses renal cancer cell proliferation, migration, and invasion

“…However, Ding et al 23 found that the relationship between expression of RBM38 and prognosis varied in different cancer tissues by bioinformatics analysis. In RCC clinical samples, we found that RBM38 was significantly down-regulated in RCC samples compared with adjacent non-tumor samples.…”

“…30,31 Recently, it has also found that the expression of RBM38 varied in different types of cancers by bioinformatics analysis. 23 However, expression and biologic functions of RBM38 in human RCC remain obscure. Moreover, there were few studies describing the relationship between the RBM38 expression and prognosis in patients who suffered from cancer.…”

“…11 The RNA-binding motif protein 38 (RBM38, also known as RNPC1) is a member of the RRM-containing RBP family, which is known to regulate messenger RNA (mRNA) translation of p53 and mRNA stability of p21, 12 Hu antigen R (HuR), 13 p63, 14 p73, 15 mouse double minute 2 homolog (MDM2), 16 macrophage inhibitory cytokine 1 (MIC-1), 17 estrogen receptors (ERs), 18 progesterone receptors (PRs), 19 and E2F1 transcripts. 20 RBM38 is frequently overexpressed in cancers, including dog lymphoma, 21 esophageal cancer, 22,23 prostate, 24,25 chronic lymphocytic leukemia, 26 and breast cancer, 18 suggesting that RBM38 may function as an oncogene. But new evidences suggested that RBM38 acts as a tumor suppressor in breast cancer, 27 ovarian cancer, 20 colorectal cancer (CRC), 28 and acute myeloid leukemia.…”