title: Comparison of hematopoietic cancer stem cells with normal stem cells leads to discovery of novel differentially expressed SSRs.
abstract: Tandem repeat expansion in the transcriptomics level has been considered as one of the underlying causes of different cancers. Cancer stem cells are a small portion of cancer cells within the main neoplasm and can remain alive during chemotherapy and re-induce tumor growth. The EST-SSR background of cancer stem cells and possible roles of expressed SSRs in altering normal stem cells to cancer ones have not been investigated yet. Here, SSR distributions in hematopoietic normal and cancer stem cells were compared based on the expressed EST-SSR. One hundred eighty nine and 223 EST-SSRs were identified in cancer and normal stem cells, respectively. The EST-SSR expression pattern was significantly different between normal and cancer stem cells. The frequencies of AC/GT and TA/TA EST-SSRs were about 10% higher in cancer than normal stem cells. Remarkably, the number of triplets in cancer stem cells was 1.5 times higher than that in normal stem cells. GAT EST-SSR was frequent in cancer stem cells, but, conversely, normal stem cells did not express GAT EST-SSR. We suggest this EST-SSR as a novel triplet in cancer stem cell induction. Translating EST-SSRs to amino acids demonstrated that Asp and Ile were more abundant in cancer stem cells compared to normal stem cells. Finally, Gene Ontology (GO) enrichment analysis was carried out on genes containing triplet SSRs and showed that SSRs intentionally visit some specific GO classes. Interestingly, a NF-kappa (nuclear factor-kB) binding transcription factor was significantly hit by SSR instability which is a hallmark for leukemia stem cells. NF-kappa is an over represented transcription factor during cancer progression. It seems that there is a crosstalk between the NF-kB transcription factor and expressed GAT tandem repeat which negatively regulate apoptosis. In addition to better understanding of tumorigenesis, the findings of this study offer new DNA markers for diagnostic purposes and identifying at risk populations. In addition, a new approach for gene discovery in cancer by target analysis of differentially expressed EST-SSRs between cancer and normal stem cells is presented here.
authors.affiliation: Iranian Research Organization for Science and Technology, Tehran, Iran.
authors.forename: Batool
authors.initials: B
authors.lastname: Hosseinpour
authors.affiliation: Department of Animal and Poultry Science, College of Aburaihan, University of Tehran, Tehran, Iran. Electronic address: mrbakhtiari@ut.ac.ir.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Bakhtiarizadeh
authors.affiliation: Iranian Research Organization for Science and Technology, Tehran, Iran.
authors.forename: Seyedeh Maryam
authors.initials: SM
authors.lastname: Mirabbassi
authors.affiliation: Institute of Biotechnology, Shiraz University, Shiraz, Iran; School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, Australia. Electronic address: esmaeil.ebrahimie@adelaide.edu.au.
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Ebrahimie
mesh_terms: D018900:Dinucleotide Repeats / Q000235:genetics; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D015723:Gene Library; D063990:Gene Ontology; D019337:Hematologic Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D016328:NF-kappa B; D009841:Oligonucleotides
keywords: Cancer stem cell; GAT triplet; Gene Ontology; NF-kappa; SSR; Tandem repeat