Абстракты статей Чехонина В.П., опубликованных в 2014 годуНазад
Абстракты статей Чехонина В.П., опубликованных в 2014 году
1. Koshkin P.A., Chistiakov D.A., Nikitin A.G.,Konovalov A.N., Potapov A.A.,Usachev D.Y., Pitskhelaury D.I., Kobyakov G.L.,Shishkina L.A., Chekhonin V.P.
Analysis of expression of microRNAs and genes involved in the control of key signaling mechanisms that support or inhibit development of brain tumors of different grades.
Clin Chim Acta. 2014 Mar 20;430:55-62.
Background:
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of key biological processes. Different miRNAs with pro-oncogenic and anti-oncogenic properties have been identified in glioblastomas. We decided to analyze expression profiles of 10 mature miRNAs (miR-7-1, miR-10а, miR-17, miR-20а, miR-21, miR-23а, miR-26а, miR-137, and miR-222) in post-surgery glioma specimens of different grades in order to find whether the expression level correlates with tumor grades. We also measured expression of six key genes such as PTEN, p21/CDKN1A, MDR1, ABCG2, BAX, and BCL-2 involved in the regulation of critical glioma signaling pathways to establish the effect of miRNAs on these signaling mechanisms.
Methods:
Using RT-PCR, we performed expression analysis of 25 tumor fresh samples (grades II-IV).
Results:
We found gradual increase in miR-21 and miR-23a levels in all tumor grades whereas miR-7 and miR-137 were significantly down-regulated depending on the glioma grade. MDR, ABCG2, and p21/CDKN1A levels were significantly up-regulated while expression of PTEN was down-regulated in tumor samples compared to the normal brain tissue.
Conclusions:
These observations provide new insights into molecular pathogenic mechanisms of glioma progression and suggest about a potential value of miRNAs as a putative diagnostic marker of brain tumors.
2. Chistiakov D.A., Chekhonin V.P.
Extracellular vesicles shed by glioma cells: pathogenic role and clinical value.
Tumour Biol. 2014, Sept.359(9),p.8425-8438
Extracellular vesicles (EVs) are commonly used by normal and tumor cells for communication at long distances to exchange by complex molecular messages and deliver a variety of essential biomolecules. EVs (exosomes and microvesicles) released in large numbers by glioma cells represent a key mechanism of intercellular signaling. Tumor-derived EVs are produced to regulate all vital functions of tumor cells including growth, proliferation, migration, survival, malignancy, invasion, and resistance to host anti-tumor immunity and anti-cancer drugs. Glioma EVs were shown to carry a variety of biomolecules such as oncogenic growth factors, receptors, enzymes, transcription factors, signaling and immunomodulatory molecules, DNA of mutated and nonmutated oncogenes, RNA transcripts, and noncoding RNA including retrotransposons, vault RNA, and microRNAs. Glioma-derived EVs can be useful as a source of potential tumor-associated biomarkers essential for development and validation of new diagnostic and prognostic tools for glioma and glioblastoma. Tumor EVs are enriched with glioma antigens that could be helpful, for example, for development of new advanced anti-tumor immune vaccines based on autologous dendritic cells stimulated by tumor-specific antigens.
3. Bryukhovetskiy A, Shevchenko V, Kovalev S, Chekhonin V, Baklaushev V, Bryukhovetskiy I, Zhukova M.
To the novel paradigm of proteome-based cell therapy of tumors: through comparative proteome mapping of tumor stem cells and tissue-specific stem cells of humans.
Cell Transplant. 2014 Oct 9. [Epub ahead of print]
We performed proteome mapping, cataloguing and bioinformation analysis of protein lysates of human neural (CD133+) progenitor and stem cells (NPSCs) isolated from the olfactory sheath of a nose, multipotent mesenchymal (CD29+, CD44+, CD73+, CD90+, CD34-) stromal cells (MMSCs) isolated from human bone marrow and tumor (CD133+) stem cells (TSCs) isolated from the human U87 glioblastoma cell line. We identified 1664 proteins in the examined lysates of stem cells (SCs), 1052 (63.2%) of which are identical in NPSCs and TSCs and 607 proteins (36.47%) of which are identical in MMSCs and TSCs. Other proteins in U87 glioblastoma TSCs are oncospecific or carcinogenesis associated. The biological processes, molecular functions, cell localization and protein signal pathways of the proteins available in all three proteomes were annotated by PubMed (http://www.ncbi.nlm.nih.gov/pubmed/), PANTHER (http://www.pantherdb.org/), GeneOntology (http://www.geneontology.org/) and KEGG (http://www.genome.jp/kegg/) databases. It was shown that gliomaspheres of U87 glioblastoma had only 10 intracellular pathways of signal transduction (IPST) that were not modified by the neoplastic process, but only two of them (integrin and focal adhesion pathways) were accessible for regulatory action on gene candidates in the TSC nucleus. Carcinogenesis free membrane proteins, IPST and genes expressing proteins of these pathways in U87 glioblastoma TSCs can be viewed as main targets for regulatory effects on TSCs. We offer a novel concept of proteome-based complex therapy of tumors. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
4. Koshkin FA, Chistyakov DA, Nikitin AG, Konovalov AN, Potapov AA, Usachyov DY, Pitskhelauri DI, Kobyakov GL, Shishkina LV, Chekhonin VP.
Profile of MicroRNA Expression in Brain Tumors of Different Malignancy.
Bull Exp Biol Med. 2014 Oct;157(6):794-7
The expression profiles of 10 mature microRNA (7, 10a, 17, 20a, 21, 23a, 26a, 137, 222) in biopsy specimens of gliomas of different malignancy were studied by the real time PCR with SYBR Green I fluorescent stain. The expression of microRNA-21 increased significantly, while that of microRNA-137 decreased, depending on the tumor malignancy. The expression of microRNA-9, -17, -20a, -23a, -26a was significantly higher, while that of microRNA-7 lower in the tumor vs. control tissue samples. New data on the molecular pathological mechanisms of gliomas related to their malignancy were obtained. Quantitative analysis of microRNA was suggested as a potential diagnostic marker of brain tumors.
5. Morozova AY, Zubkov EA, Koshkin FA, Storozheva ZI, Chekhonin VP.
Expression of genes encoding serotonin receptors and SERT in various brain structures of stressed rats after chronic exposure to ultrasound.
Bull Exp Biol Med. 2014 Jan;156(3):317-9.
The expression of genes encoding serotonin receptors and serotonin transporter in emotiogenic structures of rat brain was shown to change after chronic stress with ultrasonic waves of varying frequencies. A QPCR-RT study revealed the increased expression of genes for SERT and 5-HT1B receptor and decreased expression of the 5-HT2A receptor in the prefrontal cortex of rats after chronic exposure to ultrasonic waves of varying frequencies. Gene expression was increased for SERT, but decreased for 5-HT1B, 5-HT2A, and 5-HT2B receptors in the midbrain of animals. The hippocampus was characterized by an increased expression of genes encoding SERT and 5-HT1A, 5-HT2A, and 5-HT2B receptors. Our results indicate that the exposure to this type of stress is followed by dysregulation in the serotoninergic system of the brain.
