Browsing by Author "Creighton, Chad J."

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Identification of miR139 as a Saliva Biomarker for Tongue Squamous Cell Carcinoma: A Pilot Study
(Springer, 2016) Duz, Mehmet Bugrahan; Karatas, Omer Faruk; Guzel, Esra; Turgut, Nesrettin Fatih; Yilmaz, Mehmet; Creighton, Chad J.; Ozen, Mustafa
Of all human oral carcinomas, 41 % are localized to the tongue. Despite considerable improvements in both diagnosis and treatment, tongue squamous cell carcinoma (TSCC) has remained one of the most lethal types of cancer. Here, we aimed at identifying a salivary microRNA (miRNA) expression signature specific for TSCC patients. To identify putative diagnostic biomarkers, we compared the miRNA expression profiles of saliva samples from three TSCC patients and four healthy control individuals using an Agilent miRNA microarray platform (V19). Three of the differentially expressed miRNAs identified were selected for further validation using quantitative reverse-transcription PCR (qRT-PCR) in saliva samples from 25 TSCC patients and 25 healthy control individuals. Through microarray-based expression profiling, we found that 419 miRNAs were deregulated in the saliva samples from the TSCC patients compared to those from the healthy control individuals tested. Subsequent qRT-PCR analysis revealed that the expression level of miR-139-5p was significantly reduced in the TSCC validation samples compared to the controls. Further analysis of post-operative saliva samples derived from TSCC patients revealed that the miR-139-5p expression levels had turned back to normal again. In addition, we found that miR-139-5p exhibited enough power to discriminate pre-operative TSCC patients from both normal individuals (AUC: 0.805) and post-operative TSCC patients (AUC: 0.713), thereby underscoring its diagnostic potential. From our results we conclude that saliva can be used as a feasible source for routine TSCC diagnostics and that miR-139-5p may serve as a potential biomarker for early TSCC detection.
Micrornas as Prognostic Markers in Prostate Cancer
(Wiley, 2019) Suer, Ilknur; Guzel, Esra; Karatas, Omer F.; Creighton, Chad J.; Ittmann, Michael; Ozen, Mustafa
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.
miR1 and miR133b Are Differentially Expressed in Patients with Recurrent Prostate Cancer
(Public Library Science, 2014) Karatas, Omer Faruk; Guzel, Esra; Suer, Ilknur; Ekici, Isin D.; Caskurlu, Turhan; Creighton, Chad J.; Ozen, Mustafa
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.
miR221 as a Pre- and Postoperative Plasma Biomarker for Larynx Cancer Patients
(Wiley, 2015) Yilmaz, Seda Salman; Guzel, Esra; Karatas, Omer Faruk; Yilmaz, Mehmet; Creighton, Chad J.; Ozen, Mustafa
Objective: In order to identify a plasma microRNA (miRNA) signature of larynx cancer (LCa), we examined miRNAs profile of plasma samples obtained from 30 LCa patients (preoperative and postoperative serum samples) and 30 healthy controls. Study Design: Basic science research study. Methods: MicroRNA profiling of eight plasma samples (four from preoperative, four from control individuals) were performed using miRNA microarray. Two of the significantly deregulated miRNAs were selected for further confirmation in the remaining samples using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: Microarray profiling and qRT-PCR analysis showed that miR-221 was upregulated in LCa plasma samples. Further qRT-PCR analysis demonstrated that miR-221 was at normal levels in postoperative plasma samples. Conclusions: Plasma miR-221 may have a potential as a novel diagnostic/prognostic marker and might be considered as a therapeutic target in LCa.
miR33a Is a Tumor Suppressor microRNA That Is Decreased in Prostate Cancer
(Impact Journals LLC, 2017) Karatas, Omer Faruk; Wang, Jianghua; Shao, Longjiang; Ozen, Mustafa; Zhang, Yiqun; Creighton, Chad J.; Ittmann, Michael
Prostate cancer is one of the most frequently diagnosed neoplasms among men worldwide. MicroRNAs (miRNAs) are involved in numerous important cellular processes including proliferation, differentiation and apoptosis. They have been found to be aberrantly expressed in many types of human cancers. They can act as either tumor suppressors or oncogenes, and changes in their levels are associated with tumor initiation, progression and metastasis. miR-33a is an intronic miRNA embedded within SREBF2 that has been reported to have tumor suppressive properties in some cancers but has not been examined in prostate cancer. SREBF2 increases cholesterol and lipid levels both directly and via miR-33a action. The levels of SREBF2 and miR-33a are correlated in normal tissues by co-transcription from the same gene locus. Paradoxically, SREBF2 has been reported to be increased in prostate cancer, which would be predicted to increase miR-33a levels potentially leading to tumor suppression. We show here that miR-33a has tumor suppressive activities and is decreased in prostate cancer. The decreased miR-33a increases mRNA for the PIM1 oncogene and multiple genes in the lipid beta-oxidation pathway. Levels of miR-33a are not correlated with SREBF2 levels, implying posttranscriptional regulation of its expression in prostate cancer.
Oncogenic miR1825 Promotes Head and Neck Carcinogenesis Via Targeting Frem1
(Wiley, 2023) Capik, Ozel; Gundogdu, Betul; Tatar, Arzu; Sahin, Abdulkadir; Chen, Fengju; Creighton, Chad J.; Karatas, Omer Faruk
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant cancer type worldwide. Although the therapeutic modalities currently used for patients with HNSCC improved in recent decades, HNSCC prognosis is still poor. Therefore, it is an urgent necessity to understand the pathogenesis of HNSCC, to develop novel and effective treatment strategies, and to characterize and identify the oncogenes that are responsible for an aggressive HNSCC phenotype. In this study, we aimed to better understand the roles of miR-1825 in the pathogenesis of HNSCC. We examined the impacts of miR-1825 deregulation on the cancer-associated phenotypes using in vitro tests evaluating cell viability, clonogenicity, cell migration, invasion, apoptosis, and stem cell characteristics. In addition, we investigated the effects of miR-1825 overexpression on the tumor formation capacity of head and neck cancer cells in vivo using nude mice. We searched for potential targets of miR-1825 using microarray analysis and luciferase assay. We found that miR-1825 expression is upregulated in head and neck cells and clinical tumor samples in comparison to corresponding controls, where it potentially acts as an oncogene. We, then, showed that ectopic miR-1825 overexpression promotes cellular phenotypes related to head and neck cancer progression in vitro and has a stimulating potential on cancer formation in vivo. We also identified FREM1 as a direct target of miR-1825 and demonstrated its reduced expression in HNSCC samples using immunohistochemistry analysis. Collectively, we suggest that the miR-1825/FREM1 axis serves as an important mediator of HNSCC development, where miR-1825 acts as an oncogene.
The Role of miR145 in Stem Cell Characteristics of Human Laryngeal Squamous Cell Carcinoma Hep-2 Cells
(Sage Publications Ltd, 2016) Karatas, Omer Faruk; Suer, Ilknur; Yuceturk, Betul; Yilmaz, Mehmet; Hajiyev, Yusif; Creighton, Chad J.; Ozen, Mustafa
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.