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The transcriptome landscape of the carcinogenic treatment response in the blind mole rat: insights into cancer resistance mechanisms

التفاصيل البيبلوغرافية
العنوان: The transcriptome landscape of the carcinogenic treatment response in the blind mole rat: insights into cancer resistance mechanisms
المؤلفون: Aaron Avivi, Irena Manov, Imad Shams, Abraham B. Korol, A. Paz, Robert Altwasser
المصدر: BMC Genomics, Vol 20, Iss 1, Pp 1-15 (2019)
BMC Genomics
بيانات النشر: Springer Science and Business Media LLC, 2019.
سنة النشر: 2019
مصطلحات موضوعية: 0106 biological sciences, Candidate gene, lcsh:QH426-470, Carcinogenesis, DNA repair, Spalax, lcsh:Biotechnology, Biology, 01 natural sciences, Transcriptome, Mice, 03 medical and health sciences, Species Specificity, Cancer-resistance, Neoplasms, lcsh:TP248.13-248.65, microRNA, Genetics, medicine, Animals, Humans, Amino Acid Sequence, Gene, Disease Resistance, Cancer, 030304 developmental biology, 0303 health sciences, High-Throughput Nucleotide Sequencing, Extracellular matrix, medicine.disease, biology.organism_classification, Gene Expression Regulation, Neoplastic, lcsh:Genetics, Fanconi anemia, Cancer cell, Carcinogens, Cancer research, Sequence Alignment, Research Article, 010606 plant biology & botany, Biotechnology
الوصف: Background Spalax, the blind mole rat, developed an extraordinary cancer resistance during 40 million years of evolution in a subterranean, hypoxic, thus DNA damaging, habitat. In 50 years of Spalax research, no spontaneous cancer development has been observed. The mechanisms underlying this resistance are still not clarified. We investigated the genetic difference between Spalax and mice that might enable the Spalax relative resistance to cancer development. We compared Spalax and mice responses to a treatment with the carcinogen 3-Methylcholantrene, as a model to assess Spalax’ cancer-resistance. Results We compared RNA-Seq data of untreated Spalax to Spalax with a tumor and identified a high number of differentially expressed genes. We filtered these genes by their expression in tolerant Spalax that resisted the 3MCA, and in mice, and found 25 genes with a consistent expression pattern in the samples susceptible to cancer among species. Contrasting the expressed genes in Spalax with benign granulomas to those in Spalax with malignant fibrosarcomas elucidated significant differences in several pathways, mainly related to the extracellular matrix and the immune system. We found a central cluster of ECM genes that differ greatly between conditions. Further analysis of these genes revealed potential microRNA targets. We also found higher levels of gene expression of some DNA repair pathways in Spalax than in other murines, like the majority of Fanconi Anemia pathway. Conclusion The comparison of the treated with the untreated tissue revealed a regulatory complex that might give an answer how Spalax is able to restrict the tumor growth. By remodeling the extracellular matrix, the possible growth is limited, and the proliferation of cancer cells was potentially prevented. We hypothesize that this regulatory cluster plays a major role in the cancer resistance of Spalax. Furthermore, we identified 25 additional candidate genes that showed a distinct expression pattern in untreated or tolerant Spalax compared to animals that developed a developed either a benign or malignant tumor. While further study is necessary, we believe that these genes may serve as candidate markers in cancer detection. Electronic supplementary material The online version of this article (10.1186/s12864-018-5417-z) contains supplementary material, which is available to authorized users.
تدمد: 1471-2164
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a03985c2473b098cafeb5afdeedafbb
https://doi.org/10.1186/s12864-018-5417-z
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....0a03985c2473b098cafeb5afdeedafbb
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14712164