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Transcriptome study in China.

The Chinese genome project was initiated in 1993 with the goal of contributing 1% to the Human Genome Program. The study of gene expression profiles with cDNA microarrays, and large-scale sequencing and analysis of 130928 expressed sequence tags (ESTs), allowed isolation and characterization of over 1000 novel full-length human cDNAs derived from human hematopoietic stem/progenitor cells, neuroendocrine tissues, liver, and cardiovascular cells. In addition, EST sequencing for model organisms, including rat, zebrafish, Schistosoma japonicum and rice was performed, aiming at identifying genes associated with physiological and/or pathological characteristics.

Animals↗

PubMed2002

Extensive oligonucleotide microarray transcriptome analysis of the rat cerebral artery and arachnoid tissue.

Cerebral vessels have certain distinct anatomical and developmental characteristics which are well known, but their characteristic genetic expression profile remains as yet only poorly understood. We investigated gene expression in the rat cerebral artery in comparison with the rat descending aorta, two locations which have obviously different anatomical and developmental characteristics. Since the contamination of cerebral small arteries by arachnoid tissue is to a certain extent inevitable, we also performed a gene expression analysis of arachnoid tissue as a background. In an effort to obtain the necessary quality and quantity of total RNA, a novel freeze-fracture apparatus minimizing the time required for the entire procedure from tissue separation to RNA preparation was used. With the material obtained, a group of genes highly expressed in each tissue was detected by oligonucleotide microarray analysis. In the circle of Willis, peptide-19 (PEP-19), connexin-37 (CXN-37), growth arrest-and DNA damage-inducible gene (GADD45), and the putative G protein coupled receptor RA1c, Notch-1, and jagged-1 were predominantly expressed. In arachnoid tissue, bone morphologic protein (BMP)-7, BMP-6, beta defensin-1, neuroendocrine protein 7B2, thiol-specific antioxidant protein, IL-18, beta-chain clathrin-associated protein complex AP-1, and angiopoietin-2 were highly expressed. In the aorta, most of the abundantly expressed genes related to lipid metabolism. By means of oligonucleotide microarray analysis, the distinct gene expression profiles in the circle of Willis arachnoid tissue, and aorta were made evident. From these findings it is reasonable to conclude that a functional interaction exists between the circle of Willis and arachnoid tissue.

Animals↗

PubMed2006

Expression profiling by whole-genome interspecies microarray hybridization reveals differential gene expression in procyclic promastigotes, lesion-derived amastigotes, and axenic amastigotes in Leishmania mexicana.

We examined the Leishmania mexicana transcriptome to identify differentially regulated mRNAs using high-density whole-genome oligonucleotide microarrays designed from the genome data of a closely related species, Leishmania major. Statistical analysis on array hybridization data representing 8156 predicted coding regions revealed 288 genes (3.5% of all genes) whose steady-state mRNA levels meet criteria for differential regulation between promastigotes and lesion-derived amastigotes. Interestingly, sample comparison of promastigotes to axenic amastigotes resulted in only 17 genes (0.2%) that meet the same statistical criteria for differential regulation. The reduced number of regulated genes is a consequence of an increase in the magnitude of the transcript levels in cells under axenic conditions. The expression data for a subset of genes was validated by quantitative PCR. Our studies show that interspecies hybridization on microarrays can be used to analyze closely related protozoan parasites, that axenic culture conditions may alter amastigote transcript abundance, and that there is only a relatively modest change in abundance of a few mRNAs between morphologically distinct promastigote and amastigote cultured cells. Leishmania may represent an alternative paradigm for eukaryotic differentiation with minimal contributions from changes in mRNA abundance.

Animals↗

PubMed2006

Catalog of gene expression in adult neural stem cells and their in vivo microenvironment.

Stem cells generally reside in a stem cell microenvironment, where cues for self-renewal and differentiation are present. However, the genetic program underlying stem cell proliferation and multipotency is poorly understood. Transcriptome analysis of stem cells and their in vivo microenvironment is one way of uncovering the unique stemness properties and provides a framework for the elucidation of stem cell function. Here, we characterize the gene expression profile of the in vivo neural stem cell microenvironment in the lateral ventricle wall of adult mouse brain and of in vitro proliferating neural stem cells. We have also analyzed an Lhx2-expressing hematopoietic-stem-cell-like cell line in order to define the transcriptome of a well-characterized and pure cell population with stem cell characteristics. We report the generation, assembly and annotation of 50,792 high-quality 5'-end expressed sequence tag sequences. We further describe a shared expression of 1065 transcripts by all three stem cell libraries and a large overlap with previously published gene expression signatures for neural stem/progenitor cells and other multipotent stem cells. The sequences and cDNA clones obtained within this framework provide a comprehensive resource for the analysis of genes in adult stem cells that can accelerate future stem cell research.

Animals↗

PubMed2005

Epidermal growth factor-induced hepatocellular carcinoma: gene expression profiles in precursor lesions, early stage and solitary tumours.

Epidermal growth factor is an important mitogen for hepatocytes. Its overexpression promotes hepatocellular carcinogenesis. To identify the network of genes regulated through EGF, we investigated the liver transcriptome during various stages of hepatocarcinogenesis in EGF2B transgenic mice. Targeted overexpression of IgEGF induced distinct hepatocellular lesions and eventually solid tumours at the age of 6-8 months, as evidenced by histopathology. We used the murine MG U74Av2 oligonucleotide microarrays to identify transcript signatures in 12 tumours of small (n=5, pooled), medium (n=4) and large sizes (n=3), and compared the findings with three nontumorous transgenic livers and four control livers. Global gene expression analysis at successive stages of carcinogenesis revealed hallmarks linked to tumour size. A comparison of gene expression profiles of nontumorous transgenic liver versus control liver provided insight into the initial events predisposing liver cells to malignant transformation, and we found overexpression of c-fos, eps-15, TGIF, IGFBP1, Alcam, ets-2 and repression of Gas-1 as distinct events. Further, when gene expression profiles of small manifested tumours were compared with nontumorous transgenic liver, additional changes were obvious and included overexpression of junB, Id-1, minopontin, villin, claudin-7, RR M2, p34cdc2, cyclinD1 and cyclinB1 among others. These genes are therefore strongly associated with tumour formation. Our study provided new information on the tumour stage-dependent network of EGF-regulated genes, and we identified candidate genes linked to tumorigenes and progression of disease.

Animals↗

PubMed2025

Transcriptome-Wide Analysis of the 5' Cap Status of RNA Using 5' Monophosphate-Dependent Exonuclease Digestion and RNA Sequencing.

Eukaryotic mRNAs carry an N7-methylguanosine (m7G) cap structure at their 5' extremity, which protects them from the degradation by 5'-3' exoribonucleases and plays a pivotal role in mRNA metabolism, promoting splicing, nuclear export, and translation. Decapping, the enzymatic process that removes this structure, is a key event during cytoplasmic mRNA 5'-3' decay, leading to the degradation of the transcript body by Xrn1. In this chapter, we describe a procedure to assess the cap status of RNA at the transcriptome level. It is based on a treatment of total RNA extracts with a 5' monophosphate-dependent exonuclease, which like Xrn1 specifically degrades decapped RNAs harboring 5' monophosphate extremities, but not RNAs with intact m7G cap. The digested RNAs are then analyzed by RNA sequencing.

Exoribonucleases↗

PubMed2026

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals↗

PubMed2026

Transcriptomic insights into the coordinated regulation of signaling, apoptosis, immunity, and metabolism during Sinonovacula constricta larval metamorphosis.

Metamorphosis is a critical ontogenetic transition for marine bivalves, marking the shift from planktonic to benthic lifestyles, where successful transformation dictates survival. The razor clam Sinonovacula constricta is economically important; however, low larval metamorphosis rates remain a major bottleneck in seedling production. To elucidate the mechanisms governing this process, we performed a comparative transcriptome analysis of S. constricta larvae at pre- and post-metamorphosis stages using Illumina sequencing. A total of 3701 differentially expressed genes (DEGs) were identified, including 3254 up-regulated and 447 down-regulated genes. Functional annotation of the respective top 20 significantly up-regulated and down-regulated DEGs indicated their potential pivotal roles in signal transduction (e.g., up-regulated: CAV1, CHRNA2; down-regulated: APP, NOTCH1), cellular proliferation and differentiation (e.g., up-regulated: TUBA, EGF1; down-regulated: KIF23, TTC25), transcriptional and epigenetic regulation (e.g., up-regulated: NFIL3; down-regulated: OVO, HMX1), substance transport (e.g., up-regulated: LRP2, LRP1B; down-regulated: SLC51A, Slc33a1), substance metabolism (e.g., up-regulated: CPK3, CYP26A1; down-regulated: RDMT1, ADAC), immunomodulation (e.g., up-regulated: CPN2, CRISP2), and protein homeostasis (e.g., up-regulated: HSP27, NAS-27). Functional enrichment analysis further revealed that DEGs were significantly enriched in pathways related to signal transduction and developmental regulation (e.g., Ras, TNF), cell death and homeostasis (e.g., apoptosis), immune responses (e.g., Toll-like receptor), energy metabolism (e.g., lipid), cardiovascular related (e.g., Fluid shear stress), cell junction and architecture (e.g., Tight junction), and infectious disease (e.g., measles). These results suggest a synergistic interplay between signaling, apoptosis, immunity, and metabolism during S. constricta metamorphosis. This study advances our understanding of marine bivalve metamorphosis and offers candidate genes for further mechanistic studies.

Animals↗

PubMed2004

The impact of transcriptome and proteome analyses on antibiotic drug discovery.

Recent scientific publications demonstrate the increasing interest in measurement of genome-wide gene expression on transcript and protein level in response to treatment with antibacterial agents. Nevertheless, the number of large bacterial transcriptome and proteome datasets available so far is limited, although a high number and diversity of antibiotic-triggered expression profiles aid to optimally exploit these technologies. The first published examples substantiate the need to establish these so-called reference compendia of bacterial expression profiles, to discover the molecular mechanism-of-action of uncharacterized bioactive substances. In addition, such compendia open up ways for novel cell-based drug screening approaches.

Anti-Bacterial Agents↗

PubMed2005

Transcriptional responses in mouse lungs induced by vaccination with Mycobacterium bovis BCG and infection with Mycobacterium tuberculosis.

Transcriptome analyses enable the assessment of signature alterations in whole tissues and organs undergoing pathological processes. We analyzed gene expression profiles of lungs from mice infected with Mycobacterium tuberculosis or vaccinated with Mycobacterium bovis bacille Calmette-Guérin (BCG). We compared high-dose systemic and low-dose aerosol M. tuberculosis infections as well as systemic BCG vaccination. Expression profiles in lungs were analyzed at day (d) 1 and d 30 post infection / vaccination using a custom tailored 'in situ' synthesized 60-mer oligonucleotide microarray with focus on immunologically relevant genes. At d 1, a small number of genes were differentially regulated, whereas at d 30, a discrete expression pattern was identified in the lung. Differential gene expression profiles between M. tuberculosis infection and BCG vaccination indicate differences in naturally and vaccine induced pulmonary immune responses. The shared signature of systemic and aerosol M. tuberculosis infection revealed dominance of genes related to or controlled by interferon gamma (IFN-gamma). We assume that differential gene expression profiles after M. tuberculosis infection are strongly influenced by differences in cellular composition of the lung due to migration of immune cells, primarily neutrophils, basophils, eosinophils and monocytes to the site of infection.

Animals↗

PubMed2003

The role of HIF-1 alpha in transcriptional regulation of the proximal tubular epithelial cell response to hypoxia.

Epithelial cells of the kidney represent a primary target for hypoxic injury in ischemic acute renal failure (ARF); however, the underlying transcriptional mechanism(s) remain undefined. In this study, human proximal tubular epithelial cells (HK-2) exposed to hypoxia in vitro demonstrated a non-lethal but dysfunctional phenotype, closely reflective of the epithelial pathobiology of ARF. HK-2 cells exposed to hypoxia demonstrated increased paracellular permeability, decreased proliferation, loss of tight junctional integrity, and significant actin disassembly in the absence of cell death. Microarray analysis of transcriptomic changes underlying this response identified a distinct cohort of 48 genes with a closely shared hypoxia-dependent expression profile. Within this hypoxia-sensitive cluster were genes identified previously as hypoxia-inducible factor-1 (HIF-1)-dependent (e.g. vascular endothelial growth factor and adrenomedullin) as well as genes not previously known to be hypoxia-responsive (e.g. stanniocalcin 2). In hypoxia, HIF-1 bound to evolutionarily conserved hypoxia-response elements (HRE) in the promoters of these genes as well as to the HRE consensus motif. A further subset of these genes, not associated with transcriptional regulation by HIF-1, was also present, suggesting alternative HIF-1-independent pathways. Overexpression of HIF-1 alpha in normoxia induced the expression of a significant number of the hypoxia-dependent genes; however, it did not induce the pathophysiologic epithelial response. In summary, hypoxia-elicited alterations in renal proximal tubular epithelial cells in vitro closely resemble the epithelial pathophysiology of ARF. Our data indicate that although this event may rely heavily on HIF-1-dependent gene transcription, it is likely that separate hypoxia-dependent transcriptional regulators also play a role.

Acute Kidney Injury↗

PubMed2005

Characterization of a normalized cDNA library from bovine intestinal muscle and epithelial tissues.

Tissue-specific cDNA library sequences (expressed sequence tags, or EST) yield a detailed snapshot of gene expression and are useful in developing second-generation molecular resources (i.e., microarrays) for gene expression profiling. The objective of this study was to develop and characterize an intestine-specific cDNA library to examine the transcriptome of the bovine gut and identify expressed genes that influence ruminant nutrition and health. We describe BARC-8BOV, a normalized cDNA library developed from mRNA isolated from four distinct intestinal locations (duodenal, jejunal and ileal small intestine, colon) of Holstein dairy cattle resulting in 19,110 5'-EST deposited into the NCBI GenBank EST database. Assembly and clustering of these 19,110 clone sequences yielded 11,208 unique elements (3,419 contigs and 7,789 singletons) with an average length of 695 base pairs. Analysis strongly suggests normalization and tissue pooling were effective at increasing the discovery rate of new bovine sequence. A total of 1,123 sequence elements not previously identified in cattle, but with similarity to known genes in other animal species, were identified and shown to be involved in numerous critical biological processes. An additional 745 transcripts were not previously represented as EST in nucleotide or protein databases, and further analysis of these could lead to the identification of gut-specific transcript variants of known genes or potentially the discovery of novel bovine genes. Of the 11,208 assembled sequences, 11,034, or 98.4%, match sequences present in the bovine DNA trace archive at NCBI, and add to a bovine EST database previously lacking significant gut tissue representation. Ultimately, these data will also contribute in efforts to annotate the bovine genome.

Animals↗

PubMed2026

scSurv: a deep generative model for single-cell survival analysis.

MOTIVATION: Single-cell omics analysis has unveiled the heterogeneity of various cell types within tumors. However, no methodology currently reveals how this heterogeneity influences cancer patient survival at single-cell resolution. Here, we introduce scSurv, combining a Cox proportional hazards model with a deep generative model of single-cell transcriptome, to estimate individual cellular contributions to clinical outcomes. RESULTS: The accuracy of scSurv was validated using both simulated and real datasets. This method identifies cells associated with favorable or adverse prognoses and extracts genes correlated with their contribution levels. In melanoma, scSurv reproduces known prognostic macrophage classifications and facilitates hazard mapping through spatial transcriptomics in renal cell carcinoma. We also identified genes consistently associated with prognosis across multiple cancers and demonstrated the applicability of this method to infectious diseases. scSurv is a novel framework for quantifying the heterogeneity of individual cellular effects on clinical outcomes. AVAILABILITY: The implementation of scSurv is available on GitHub (https://github.com/3254c/scSurv) and Zenodo (https://doi.org/10.5281/zenodo.17793054).

Humans↗

PubMed2025

Investigating the genomic landscape of mouse models of breast cancer metastasis.

Metastasis remains a major cause of cancer mortality. AbstractThis study, expanding upon previous findings in the MMTV-PyMT model, investigated four independent mouse models, representing luminal (MMTV-PyMT, MMTV-Myc), HER2-amplified (MMTV-Her2) and triple negative (C3(1)TAg) breast cancer subtypes. Consistent with previous results, limited evidence for metastasis-associated somatic point mutations was found for all models. We also found that oncogenic drivers significantly influenced the number and size of metastasis-specific copy number variations (MSCNVs), but common driver-independent MSCNVs were rare. Furthermore, analyzing a cohort with varying genetic backgrounds while maintaining a constant oncogenic driver (PyMT) revealed that genetic background profoundly impacts MSCNVs. Transcriptome analysis demonstrated that oncogenic drivers strongly shaped metastasis-specific gene expression (MSGE), with each driver exhibiting distinct expression profiles. In contrast, MSGE in the PyMT-F1 cohort was more variable across strains. Despite the diversity of MSCNV and MSGE, functional analysis revealed that both mechanisms converge on the modulation of key cellular processes, including immune responses, metabolism, and extracellular matrix interactions. These findings emphasize the complex interplay between oncogenic drivers and genetic background in shaping the genomic and transcriptional landscapes of metastatic lesions.

Journal Article↗

PubMed2026

Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.

The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (p values ranged from 2.50 × 10-88 to 9.97 × 10-04). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (n = 362,286, all p < 0.05). Gene-drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (p = 7.08 × 10-08). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.

Humans↗

PubMed2026

Transcriptomic and proteomic signatures underlying nymphal adaptation and foam production in the forage pest Mahanarva spectabilis.

The spittlebug Mahanarva spectabilis (Distant, 1909) (Hemiptera: Cercopidae) is an important pest of forage grasses in South America, where its nymphs cause pasture damage by feeding on xylem sap and producing a characteristic foam that protects them against environmental stressors. To investigate the molecular basis of this adaptation, we integrated RNA-seq analysis of nymphs with LC-MS/MS proteomics of the Batelli gland, the primary source of foam secretion. De novo assembly of 100,666 unigenes revealed broad functional diversity, with strong representation of detoxification enzymes (CYP450s, GSTs, UGTs, carboxylesterases), transporters and ion pumps, cuticle proteins, and stress- and immunity-related genes. Nearly 16% of loci exhibited alternative splicing, particularly within detoxification, chemosensory and osmoregulatory gene families, highlighting evidence of transcriptomic variability. Signal peptide and secreted protein predictions identified 168 high-confidence candidate secreted proteins, including detoxification enzymes, proteases, structural proteins and immune-related factors, several of which are consistent with antimicrobial and surfactant-related functions. Proteomic profiling of the Batelli gland confirmed 500 proteins, enriched in chaperones, metabolic enzymes, detoxification pathways and osmoregulatory components, with the most abundant proteins corresponding to Hsp70 chaperones, ATP synthases, cuticle proteins and carbonic anhydrases. Together, these results provide an integrative transcriptomic and proteomic overview for M. spectabilis nymphs, highlighting genes and proteins associated with xylem feeding, foam production and responses potentially related to environmental stress tolerance. This comprehensive dataset not only advances the understanding of spittlebug biology but also identifies candidate molecular targets that may inform innovative strategies for controlling nymphal stages and mitigating spittlebug damage in forage systems.

Animals↗

PubMed2005

Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure.

Cardiomyopathy can be initiated by many factors, but the pathways from unique inciting mechanisms to the common end point of ventricular dilation and reduced cardiac output are unclear. We previously described a microarray-based prediction algorithm differentiating nonischemic (NICM) from ischemic cardiomyopathy (ICM) using nearest shrunken centroids. Accordingly, we tested the hypothesis that NICM and ICM would have both shared and distinct differentially expressed genes relative to normal hearts and compared gene expression of 21 NICM and 10 ICM samples with that of 6 nonfailing (NF) hearts using Affymetrix U133A GeneChips and significance analysis of microarrays. Compared with NF, 257 genes were differentially expressed in NICM and 72 genes in ICM. Only 41 genes were shared between the two comparisons, mainly involved in cell growth and signal transduction. Those uniquely expressed in NICM were frequently involved in metabolism, and those in ICM more often had catalytic activity. Novel genes included angiotensin-converting enzyme-2 (ACE2), which was upregulated in NICM but not ICM, suggesting that ACE2 may offer differential therapeutic efficacy in NICM and ICM. In addition, a tumor necrosis factor receptor was downregulated in both NICM and ICM, demonstrating the different signaling pathways involved in heart failure pathophysiology. These results offer novel insight into unique disease-specific gene expression that exists between end-stage cardiomyopathy of different etiologies. This analysis demonstrates that transcriptome analysis offers insight into pathogenesis-based therapies in heart failure management and complements studies using expression-based profiling to diagnose heart failure of different etiologies.

Angiotensin-Converting Enzyme 2↗

PubMed2007

Expression of BRCC3, a novel cell cycle regulated molecule, is associated with increased phospho-ERK and cell proliferation.

Raf-1 protein serine/threonine kinase plays an important role in ERK signal transduction pathway of cell survival and proliferation. Raf-induced transcriptional changes are dependent on phosphorylation/activation of ERK. However, regulation of phospho-ERK (p-ERK) via Raf transcriptome is as yet unknown. We report the initial characterization of BRCC3, a novel gene discovered previously by mRNA expression profiling in MDA-MB 231 human breast cancer cells treated with Raf antisense oligonucleotide. BRCC3 is localized at human chromosome 5q12.1. BRCC3 open reading frame consists of 529 amino acids, coding for an approximate 60-kDa predominantly membrane-associated protein. Expression levels of BRCC3 mRNA and protein are high during G2/M phase of the cell cycle in breast cancer cells. Treatment of MDA-MB 231 cells with Raf-1 siRNA resulted in decreased expression of Raf-1, BRCC3 and p-ERK, but not B-Raf. Transient or stable expression of the epitope-tagged BRCC3 cDNA was associated with increased p-ERK in three different cell lines. Consistently, BRCC3 siRNA treatment of MDA-MB 231 cells caused decreased expression of BRCC3 and p-ERK. Furthermore, exogenous BRCC3 expression was associated with a delay in etoposide-induced cell death and an increase in cell proliferation. These findings demonstrate that BRCC3 is a novel effector of Raf-1, and implicate a role of BRCC3 in modulation of p-ERK, cell survival and proliferation.

Amino Acid Sequence↗