The TGF-beta — SMAD pathway is inactivated in cronic lymphocytic leukemia cells

Aim: To study the status of the tumor growth factor beta (TGFB) pathway in chronic lymphocytic leukemia (CLL) cells and to uncover molecular details underlying CLL cell genesis. Objects and Methods: The study was conducted on peripheral blood samples of patients with CLL using the following methods: RNA isolation, analysis of expression of transcription factors using RT2 profiler assay, bioinformatics analysis of publicly available data bases on expression. Results: We have shown that the TGFB — SMAD canonical pathway is not active in CLL cells. SMAD-responsive genes, such as BCL2L1 (BCL-XL), CCND2 (Cyclin D2), and MYC, are down-regulated in CLL cells compared with peripheral blood B cells of healthy donors. Conclusions: The TGFB-mediated signaling is not active in CLL cells due to low (or absent) expression of SMAD1, -4, -5, -9, and ATF-3. Expression and phosphorylation status of SMAD2 and -3 should be further elucidated in the future studies

The TGF-beta — SMAD pathway is inactivated in cronic lymphocytic leukemia cells

Aim: To study the status of the tumor growth factor beta (TGFB) pathway in chronic lymphocytic leukemia (CLL) cells and to uncover molecular details underlying CLL cell genesis. Objects and Methods: The study was conducted on peripheral blood samples of patients with CLL using the following methods: RNA isolation, analysis of expression of transcription factors using RT2 profiler assay, bioinformatics analysis of publicly available data bases on expression. Results: We have shown that the TGFB — SMAD canonical pathway is not active in CLL cells. SMAD-responsive genes, such as BCL2L1 (BCL-XL), CCND2 (Cyclin D2), and MYC, are down-regulated in CLL cells compared with peripheral blood B cells of healthy donors. Conclusions: The TGFB-mediated signaling is not active in CLL cells due to low (or absent) expression of SMAD1, -4, -5, -9, and ATF-3. Expression and phosphorylation status of SMAD2 and -3 should be further elucidated in the future studies

Overexpression of MRPS18-2 in cancer cell lines results in appearance of multinucleated cells

Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Human mitochondrial ribosomal protein MRPS18-2 (S18-2) is encoded by a cellular gene that is located on the human chromosome 6p21.3. We discovered that overexpression of the S18-2 protein led to immortalization and de-differentiation of primary rat embryonic fibroblasts. Cells showed anchorage-independent growth pattern. Moreover, pathways characteristic for rapidly proliferating cells were upregulated then. It is possible that the S18-2 overexpression induced disturbance in cell cycle regulation. We found that overexpression of S18-2 protein in human cancer cell lines led to an appearance of multinucleated cells in the selected clones.publishersversionPeer reviewe

Mandatory chromosomal segment balance in aneuploid tumor cells

Copyright: Copyright 2013 Elsevier B.V., All rights reserved.Background: Euploid chromosome balance is vitally important for normal development, but is profoundly changed in many tumors. Is each tumor dependent on its own structurally and numerically changed chromosome complement that has evolved during its development and progression? We have previously shown that normal chromosome 3 transfer into the KH39 renal cell carcinoma line and into the Hone1 nasopharyngeal carcinoma line inhibited their tumorigenicity. The aim of the present study was to distinguish between a qualitative and a quantitative model of this suppression. According to the former, a damaged or deleted tumor suppressor gene would be restored by the transfer of a normal chromosome. If so, suppression would be released only when the corresponding sequences of the exogenous normal chromosome are lost or inactivated. According to the alternative quantitative model, the tumor cell would not tolerate an increased dosage of the relevant gene or segment. If so, either a normal cell derived, or, a tumor derived endogenous segment could be lost. Methods: Fluorescence in Situ Hybridization based methods, as well as analysis of polymorphic microsatellite markers were used to follow chromosome 3 constitution changes in monochromosomal hybrids. Results: In both tumor lines with introduced supernumerary chromosomes 3, the copy number of 3p21 or the entire 3p tended to fall back to the original level during both in vitro and in vivo growth. An exogenous, normal cell derived, or an endogenous, tumor derived, chromosome segment was lost with similar probability. Identification of the lost versus retained segments showed that the intolerance for increased copy number was particularly strong for 3p14-p21, and weaker for other 3p regions. Gains in copy number were, on the other hand, well tolerated in the long arm and particularly the 3q26-q27 region. Conclusion: The inability of the cell to tolerate an experimentally imposed gain in 3p14-p21 in contrast to the well tolerated gain in 3q26-q27 is consistent with the fact that the former is often deleted in human tumors, whereas the latter is frequently amplified. The findings emphasize the importance of even minor changes in copy number in seemingly unbalanced aneuploid tumors.publishersversionPeer reviewe

Accurate molecular classification of cancer using simple rules

<p>Abstract</p> <p>Background</p> <p>One intractable problem with using microarray data analysis for cancer classification is how to reduce the extremely high-dimensionality gene feature data to remove the effects of noise. Feature selection is often used to address this problem by selecting informative genes from among thousands or tens of thousands of genes. However, most of the existing methods of microarray-based cancer classification utilize too many genes to achieve accurate classification, which often hampers the interpretability of the models. For a better understanding of the classification results, it is desirable to develop simpler rule-based models with as few marker genes as possible.</p> <p>Methods</p> <p>We screened a small number of informative single genes and gene pairs on the basis of their depended degrees proposed in rough sets. Applying the decision rules induced by the selected genes or gene pairs, we constructed cancer classifiers. We tested the efficacy of the classifiers by leave-one-out cross-validation (LOOCV) of training sets and classification of independent test sets.</p> <p>Results</p> <p>We applied our methods to five cancerous gene expression datasets: leukemia (acute lymphoblastic leukemia [ALL] vs. acute myeloid leukemia [AML]), lung cancer, prostate cancer, breast cancer, and leukemia (ALL vs. mixed-lineage leukemia [MLL] vs. AML). Accurate classification outcomes were obtained by utilizing just one or two genes. Some genes that correlated closely with the pathogenesis of relevant cancers were identified. In terms of both classification performance and algorithm simplicity, our approach outperformed or at least matched existing methods.</p> <p>Conclusion</p> <p>In cancerous gene expression datasets, a small number of genes, even one or two if selected correctly, is capable of achieving an ideal cancer classification effect. This finding also means that very simple rules may perform well for cancerous class prediction.</p

Positioning Europe for the EPITRANSCRIPTOMICS challenge

The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group