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Highly expressed genes in multiple myeloma cells - what can they tell us about the disease?

ABSTRACT: Cancer cells can convert proto-oncoproteins into oncoproteins by increasing the expression of genes that are oncogenic when expressed at high levels. Such genes can promote oncogenesis without being mutated. To find overexpressed genes in cancer cells from patients with multiple myeloma, we retrieved mRNA expression data from the CoMMpass database and ranked genes by their expression levels. We grouped the most highly expressed genes based on a set of criteria and we discuss the role a selection of them can play in the disease pathophysiology. The list was highly concordant with a similar list based on mRNA expression data from the PADIMAC study. Many well-known "myeloma genes" such as MCL1, CXCR4, TNFRSF17, SDC1, SLAMF7, PTP4A3, and XBP1 were identified as highly expressed, and we believe that hitherto unrecognized key players in myeloma pathogenesis are also enriched on the list. Highly expressed genes in malignant plasma cells that were absent or expressed at only a low level in healthy plasma cells included IFI6, IFITM1, PTP4A3, SIK1, ALDOA, ATP5MF, ATP5ME, and PSMB4. The ambition of this article is not to validate the role of each gene but to serve as a guide for studies aiming at identifying promising treatment targets.

SUBMITTER: Borset M

PROVIDER: S-EPMC9310595 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Highly expressed genes in multiple myeloma cells - what can they tell us about the disease?

Børset Magne M Elsaadi Samah S Vandsemb Esten N EN Hess Eli Svorkdal ES Steiro Ida J IJ Cocera Fernandez Miguel M Sponaas Anne-Marit AM Abdollahi Pegah P

European journal of haematology 20220320 1

Cancer cells can convert proto-oncoproteins into oncoproteins by increasing the expression of genes that are oncogenic when expressed at high levels. Such genes can promote oncogenesis without being mutated. To find overexpressed genes in cancer cells from patients with multiple myeloma, we retrieved mRNA expression data from the CoMMpass database and ranked genes by their expression levels. We grouped the most highly expressed genes based on a set of criteria and we discuss the role a selection ...[more]

PMID: 35276027

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Project description:BackgroundThe male germ line in flowering plants is initiated within developing pollen grains via asymmetric division. The smaller cell then becomes totally encased within a much larger vegetative cell, forming a unique "cell within a cell structure". The generative cell subsequently divides to give rise to two non-motile diminutive sperm cells, which take part in double fertilization and lead to the seed set. Sperm cells are difficult to investigate because of their presence within the confines of the larger vegetative cell. However, recently developed techniques for the isolation of rice sperm cells and the fully annotated rice genome sequence have allowed for the characterization of the transcriptional repertoire of sperm cells. Microarray gene expression data has identified a subset of rice genes that show unique or highly preferential expression in sperm cells. This information has led to the identification of cis-regulatory elements (CREs), which are conserved in sperm-expressed genes and are putatively associated with the control of cell-specific expression.FindingsWe aimed to identify the CREs associated with rice sperm cell-specific gene expression data using in silico prediction tools. We analyzed 1-kb upstream regions of the top 40 sperm cell co-expressed genes for over-represented conserved and novel motifs. Analysis of upstream regions with the SIGNALSCAN program with the PLACE database, MEME and the Mclip tool helped to find combinatorial sets of known transcriptional factor-binding sites along with two novel motifs putatively associated with the co-expression of sperm cell-specific genes.ConclusionsOur data shows the occurrence of novel motifs, which are putative CREs and are likely targets of transcriptional factors regulating sperm cell gene expression. These motifs can be used to design the experimental verification of regulatory elements and the identification of transcriptional factors that regulate sperm cell-specific gene expression.

Project description:Background and aimsPhosphoenolpyruvate (PEP) carboxylase (PEPC) catalyses the irreversible carboxylation of PEP with bicarbonate to produce oxaloacetate. This reaction powers the carbon-concentrating mechanism (CCM) in plants that perform C4 photosynthesis. This CCM is generally driven by a single PEPC gene product that is highly expressed in the cytosol of mesophyll cells. We found two C4 grasses, Panicum miliaceum and Echinochloa colona, that each have two highly expressed PEPC genes. We characterized the kinetic properties of the two most abundant PEPCs in E. colona and P. miliaceum to better understand how the enzyme's amino acid structure influences its function.MethodsCoding sequences of the two most abundant PEPC proteins in E. colona and P. miliaceum were synthesized by GenScript and were inserted into bacteria expression plasmids. Point mutations resulting in substitutions at conserved amino acid residues (e.g. N-terminal serine and residue 890) were created via site-directed PCR mutagenesis. The kinetic properties of semi-purified plant PEPCs from Escherichia coli were analysed using membrane-inlet mass spectrometry and a spectrophotometric enzyme-coupled reaction.Key resultsThe two most abundant P. miliaceum PEPCs (PmPPC1 and PmPPC2) have similar sequence identities (>95 %), and as a result had similar kinetic properties. The two most abundant E. colona PEPCs (EcPPC1 and EcPPC2) had identities of ~78 % and had significantly different kinetic properties. The PmPPCs and EcPPCs had different responses to allosteric inhibitors and activators, and substitutions at the conserved N-terminal serine and residue 890 resulted in significantly altered responses to allosteric regulators.ConclusionsThe two, significantly expressed C4Ppc genes in P. miliaceum were probably the result of genomes combining from two closely related C4Panicum species. We found natural variation in PEPC's sensitivity to allosteric inhibition that seems to bypass the conserved 890 residue, suggesting alternative evolutionary pathways for increased malate tolerance and other kinetic properties.

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Highly expressed genes in multiple myeloma cells - what can they tell us about the disease?

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Highly expressed genes in multiple myeloma cells - what can they tell us about the disease?

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