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Galloway-Mowat syndrome (GAMOS) is a very rare condition characterized by early-onset nephrotic syndrome and microcephaly with variable neurologic features. While considerable genetic heterogeneity of GAMOS has been identified, the majority of cases are caused by pathogenic variants in genes encoding the four components of the Kinase, endopeptidase, and other proteins of small size (KEOPS) complex, one of which is TP53RK. Here we describe a 3-year-old male with progressive microcephaly, neurodevelopmental deficits, and glomerular proteinuria. He was found to carry a novel homozygous TP53RK missense variant, c.163CG (p.Arg55Gly), which was considered as potentially disease-causing. We generated a morpholino tp53rk knockdown model in Xenopus laevis showing that the depletion of endogenous Tp53rk caused abnormal eye and head development. This phenotype could be rescued by the expression of human wildtype TP53RK but not by the c.163CG mutant nor by another previously described GAMOS-associated mutant c.125GA (p.Gly42Asp). These findings support the pathogenic role of the novel TP53RK variant.

Purpose: Plasma Cell Dyscrasias are a heterogeneous group of hematological diseases. The candidate ten genes identified from our transcriptome data are highly valuable and specific. Methods: We investigated the prognostic biomarker status of these genes in Plasma Cell Dyscrasias. Expression levels of ISG20, EEF2, TRIB1, RRBP1, TMED9, KDELR1, DNAJC1, DPP7, COPE and LMAN2 genes were measured via qRT-PCR from bone marrow samples of 38 Multiple Myeloma, 23 MGUS and 16 control groups. Results: According to our results, in the Multiple Myeloma group, all genes were more highly expressed than control and MGUS groups (pDNAJC1 is an important risk factor for MM (pTMED9 gene expression and clinical parameters of urea, Ca, albumin, LDH, and IGA levels (pTMED9gene in our results sheds light on myeloma genesis. Conclusion: This study contributed significantly to the search on prognostic biomarkers for Multiple Myeloma progression from MGUS and for starting early treatment in MGUS.

Objective: The production of normal blood cells in the bone marrow is interrupted in AML, which is characterized by the proliferation and accumulation of leukemic blasts. Therefore, patients experience anemia and thrombocytopenia. When gene expression of Aurora kinases, which is reported to be highly expressed in AML, decreases, it may be possible to alleviate the clinical findings in AML. In this study, it was aimed to examine the relationship of AURKB with important miRNAs that have the potential to regulate gene expression. Method: HL60 and NB4 cells were transfected with important tumor suppressor miRNAs miR-34a-5p and let-7b-5p mimics. Then, its effects on proliferation were examined with WST-8 technique and its effects on AURKB gene expression were examined with qRT-PCR. Results: It was determined that these miRNAs negatively regulated proliferation in both AML cell lines and downregulated the expression level of the Aurora kinase B (AURKB) gene in the miRNA transfected group compared to the control group. Conclusion: In conclusion, it was determined that miR-34a-5p and let-7b-5p could regulate AURKB expression in AML cells. Therefore, it was thought that these miRNAs may have an important potential as a therapeutic biomarker in preventing excessive cell division and poor prognosis in AML.

ObjectiveBreast cancer (BC) is a heterogeneous type of cancer that occurs as a result of distinct molecular alterations in breast tissue. Although there are many new developments in treatment and targeted therapy for BC in recent years, this cancer type is still the most common one among women with high morbidity and mortality. Therefore, new research is still needed for biomarker detection.MethodsGSE101124 and GSE182471 datasets were obtained from Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (circRNAs). The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used to identify the significantly dysregulated microRNAs (miRNAs) and genes considering the Prediction Analysis of Microarray (PAM50) classification. The circRNA-miRNA-gene relationship was investigated using the Cancer Specific CircRNA (v2.0) (CSCD), miRDB, miRWalk and miRTarBase databases. The circRNA–miRNA–mRNA regulatory network was constructed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation. The protein-protein interaction network was constructed by the STRING 2021 database and visualized by the Cytoscape tool (v3.9.0). Then, raw miRNA data and genes were filtered using some selection criteria according to a specific expression level in PAM50 subgroups. A bottleneck method was utilized to obtain highly interacted hub genes using cytoHubba Cytoscape plugin. The overall survival (OS) and disease-free survival (DFS) analysis were performed for these hub genes, which are detected within the miRNA and circRNA axis in our study.ResultsWe identified three circRNAs, three miRNAs, and eighteen candidate target genes that may play an important role in BC. In addition, it has been determined that these molecules can be useful in the classification of BC, especially in determining the basal-like breast cancer (BLBC) subtype.ConclusionsWe conclude that hsa_circ_0000515/ miR-486-5p/ SDC1 axis may be an important biomarker candidate in distinguishing patients in the BLBC group, especially according to the PAM50 classification of BC.

Background Prostate cancer (PCa) is the most commonly diagnosed malignancy in men who are especially over the age of 50 years in the western countries. Currently used therapeutic modalities mostly fail to give positive clinical outcomes and nearly 30% of the PCa patients eventually develop clinical recurrence. Therefore, understanding the underlying mechanisms of PCa progression is of paramount importance to help determining the course of disease. In this study, we aimed at profiling the differentially expressed microRNAs in recurrent PCa samples. Methods We profiled the microRNA expression of 20 recurrent and 20 non-recurrent PCa patients with microRNA microarray, and validated the differential expression of significantly deregulated microRNAs in 40 recurrent and 39 non-recurrent PCa specimens using quantitative reverse-transcription PCR (qRT-PCR). Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic (ROC) analysis. Results Our results demonstrated that a total of 682 probes were significantly deregulated in recurrent versus non-recurrent PCa specimen comparison. Among those, we confirmed the significant downregulation of miR-424 and upregulation of miR-572 with further qRT-PCR analysis in a larger sample set. Further ROC analysis showed that these microRNAs have enough power to distinguish recurrent specimens from non-recurrent ones on their own. Conclusions Here, we report that differential expression of miR-424 and miR-572 in recurrent PCa specimens can serve as novel biomarkers for prediction of PCa progression.

DNA methylation is an epigenetic event that is defined as the binding of a methyl group via DNA methyl transferases (DNMTs) to the fifth carbon of cytosine in the CpG dinucleotide. Regulation of the expressions of tissue-specific genes, regulation of gene expressions during development, X inactivation and imprinting events are caused by DNA methylation. The aberrant DNA methylation associated with various diseases, especially cancers, is one of the most studied epigenetic mechanisms. Decitabine, a nucleoside analogue, inhibits DNMT enzymes and causes hypomethylation in the genome. There are many studies investigating the aberrant DNA methylation status in the genome of cells treated with Decitabine. Karyotype analysis is a cytogenetic method, which has been used successfully for the detection of both numerical and structural chromosomal abnormalities for many years. Hep-2 is a laryngeal cancer cell line, which is, used to investigate various genetic and epigenetic changes at the molecular level that revealed important information about the initiation and development of laryngeal cancer. However, the number of studies showing the chromosomal structure of Hep-2 cells is insufficient. The effects of Decitabine on cell morphology in different cell lines, its relationship with proliferation of the cells and its effects on chromosomes have been studied. However, the number of studies showing the effect of Decitabine at the chromosomal level in Hep-2 cell lines is also very limited. In current study, we investigated the chromosomes of Hep-2 cells cultured 72 hours with 1 μM and 10 μM Decitabine and without Decitabine. Keywords : Cell lines, Hep-2 cell line, Karyotyping, Decitabine, DNA methylation DOI : 10.7176/JSTR/5-4-11

Infertility is an important health problem affecting 15% of couples worldwide. Intellectual disability (ID) is characterized with significant impairment of intellectual function, adaptive daily life skills and social skills. Insertion is a rare chromosomal rearrangement causing infertility and ID. Here, we report a 39-year-old man presenting with primary infertility and mild ID. The patient’s spermiogram was consistent with azoospermia. Conventional cytogenetic analysis showed a novel inversion/insertion type of chromosomal aberration involving chromosomes 18 and 2: 46, XY, inv ins(18;2)(q11.2;q13q22). We carried out the array comparative genomic hybridization analysis to confirm the cytogenetic findings. Y micro-deletion analysis demonstrated that the AZF region as intact. We suggest that the novel insertion found in this case [46, XY, inv ins(18;2)(q11.2;q13q22)] may have caused infertility and mild ID in our patient. To the best of our knowledge, this chromosomal insertion has not previously been reported.

We thank Yiqun Zhang for technical assistance in microarray analysis. The studies presented in this manuscript were partially supported by The Scientific and Technological Research Council of Turkey (TUBITAK, grant number 210T009) and by the US National Cancer Institute grant P30CA125123., The cancer stem-like cells (CSLCs) are tumorigenic cells promoting initiation, progression, and spread of the tumor. Accumulating evidences suggested the presence of CSLCs in distinct tumors including laryngeal squamous cell carcinoma (LSCC). MicroRNAs have been proposed as significant regulators of carcinogenesis, and several of them have been demonstrated to have direct roles in survival of CSLCs. In this study, we aimed to explore the role of miR-145, which is downregulated in LSCC, on cancer stem cell potency of laryngeal cancer cells. We initially showed the downregulation of miR-145 expression in tumor tissue samples and in CD133-enriched CSLCs. Quantitative reverse-transcription PCR (qRT-PCR) analysis of miR-145-transfected Hep-2 cells demonstrated the inhibitory role of miR-145 on stem cell markers like SOX2, OCT4, KLF4, and ABCG2. We, then, investigated the stem cell features of miR-145-overexpressing Hep-2 cells by sphere formation assay, single-cell cloning assay, and aldehyde dehydrogenase (ALDH) assay, which all demonstrated the inhibition of stem cell potency upon miR-145 overexpression. Further qRT-PCR analysis demonstrated altered expression of epithelial to mesenchymal transition markers in miR-145-overexpressing Hep-2 cells. In conclusion, we demonstrated the regulatory role of miR-145 in stem cell characteristics of Hep-2 cells. Based on these results, we propose that miR-145 might carry crucial roles in LSCC tumorigenesis, prognosis, metastasis, chemoresistance, and recurrence through regulating stem cell properties of tumor cells., Scientific and Technological Research Council of Turkey (TUBITAK) [210T009]; US National Cancer Institute [P30CA125123]

Larynx cancer (LCa) is an aggressive malignancy, which is the second most common malignant neoplasm of head and neck squamous cell carcinoma. Its incidences have been reported to increase and therapeutic options mostly fail to give positive clinical response especially for the advanced LCa cases. In this study we aimed to isolate stem-like cells from freshly resected LCa tumor specimens and characterize them by quantitative real time PCR (qRT-PCR) for expression of cancer stem cell markers including SOX2, OCT4, KLF4, ABCG2, CXCR4 and CD44. Our results showed that CD133(high) cells directly isolated from freshly resected tumor specimens exhibit elevated levels of SOX2, OCT4 and KLF4, and have increased expression levels of ABCG2 and CXCR4, which were associated with resistance of tumors to regular chemotherapeutic reagents. In conclusion, this study offers a useful approach utilizing CD133 to isolate stem cells directly from fresh tissues, which gives the opportunity to develop novel therapeutic tools specifically targeting these cells through their further characterization.

Background Emerging evidences proposed that microRNAs are associated with regulation of distinct physio-pathological processes including development of normal stem cells and carcinogenesis. In this study we aimed to investigate microRNA profile of cancer stem-like cells (CSLCs) isolated form freshly resected larynx cancer (LCa) tissue samples. Methods CD133 positive (CD133+) stem-like cells were isolated from freshly resected LCa tumor specimens. MicroRNA profile of 12 pair of CD133+ and CD133− cells was determined using microRNA microarray and differential expressions of selvected microRNAs were validated by quantitative real time PCR (qRT-PCR). Results MicroRNA profiling of CD133+ and CD133− LCa samples with microarray revealed that miR-26b, miR-203, miR-200c, and miR-363-3p were significantly downregulated and miR-1825 was upregulated in CD133+ larynx CSLCs. qRT-PCR analysis in a total of 25 CD133+/CD133− sample pairs confirmed the altered expressions of these five microRNAs. Expressions of miR-26b, miR-200c, and miR-203 were significantly correlated with miR-363-3p, miR-203, and miR-363-3p expressions, respectively. Furthermore, in silico analysis revealed that these microRNAs target both cancer and stem-cell associated signaling pathways. Conclusions Our results showed that certain microRNAs in CD133+ cells could be used as cancer stem cell markers. Based on these results, we propose that this panel of microRNAs might carry crucial roles in LCa pathogenesis through regulating stem cell properties of tumor cells. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2863-3) contains supplementary material, which is available to authorized users.

This work was partially supported by The Scientific and Technological Research Council of Turkey (TUBITAK) (grant number: 210T009)., Objective: Head and neck cancer is the sixth most common cancer in worldwide with an increasing incidence rate in recent years. LOXL4 is expressed in several tissues, and its expression has been shown to display a significant correlation with local lymph node metastasis. In this study, we aimed to explore the LOXL4 expression level in metastatic and non-metastatic LSCC tissues and to determine its prognostic significance. Study design: Basic science research study. Setting: University hospital. Participants: A total of 40 patients were included in the study. Main outcome measure: LOXL4 expression status in metastatic, non-metastatic LSCC and normal tissue samples was investigated by quantitative reverse-transcription PCR. Results: We demonstrated that LOXL4 was significantly overexpressed in LSCC tumour tissue samples in comparison with the corresponding normal tissues (P < 0.001); however, no significant relationship has been found between LOXL4 expression and either the metastatic potential or the T classification of the specimens. Conclusions: Although expression of LOXL4 is not statistically associated with neck metastases, we showed that LOXL4 expression significantly increased in laryngeal cancer., Scientific and Technological Research Council of Turkey (TUBITAK) [210T009]

This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) (grant number 108S051), as well as in part by the United States' National Institute of Health (CJC and MI, grant P30 CA125123). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Prostate cancer (PCa) is currently the most frequently diagnosed malignancy in the western countries. It is more prevalent in older men with 75% of the incident cases above 65 years old. After radical prostatectomy, approximately 30% of men develop clinical recurrence with elevated serum prostate-specific antigen levels. Therefore, it is important to unravel the molecular mechanisms underlying PCa progression to develop novel diagnostic/therapeutic approaches. In this study, it is aimed to compare the microRNA (miRNA) profile of recurrent and non-recurrent prostate tumor tissues to explore the possible involvement of miRNAs in PCa progression. Total RNA from 41 recurrent and 41 non-recurrent PCa tissue samples were used to investigate the miRNA signature in PCa specimens. First of all, 20 recurrent and 20 non-recurrent PCa samples were profiled using miRNA microarray chips. Of the differentially expressed miRNAs, miR-1, miR-133b and miR-145* were selected for further validation with qRT-PCR in a different set of 21 recurrent and 21 non-recurrent PCa samples. Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic analysis. Our results demonstrated that miR-1 and mir-133b have been significantly downregulated in recurrent PCa specimens in comparison to non-recurrent PCa samples and have sufficient power to distinguish recurrent specimens from non-recurrent ones on their own. Here, we report that the relative expression of miR-1 and mir-133b have been significantly reduced in recurrent PCa specimens in comparison to non-recurrent PCa samples, which can serve as novel biomarkers for prediction of PCa progression., Scientific and Technological Research Council of Turkey (TUBITAK) [108S051]; United States' National Institute of Health [P30 CA125123]