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Öğe Analysis of ROMO1 Expression Levels and Its Oncogenic Role in Gastrointestinal Tract Cancers(MDPI, 2024) Yaman, Selcuk; Akidan, Osman; Vatansever, Mehmet; Misir, Sema; Yaman, Serap OzerGastrointestinal tract cancers account for approximately one-third of cancer-related deaths. Early diagnosis and effective treatment are the most important ways to prevent cancer-related morbidity and mortality. ROMO1 has been shown to play an important role in many types of cancer. However, the biological function of ROMO1 is still poorly understood in gastrointestinal system cancers. The aim of this study is to reveal the expression change and oncogenic role of ROMO in gastrointestinal system cancers. Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, TIMER, GeneMANIA, TISIDB, and STRING were applied to assess the biological function of ROMO1 in gastrointestinal cancers (colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), pancreatic adenocarcinoma (PAAD), and stomach adenocarcinoma (STAD)). ROMO1 is significantly increased in COAD, ESCA, LUHC, and PAAD, and the overexpression of ROMO1 is associated with clinicopathological features. In addition, ROMO1 has been found to be closely associated with tumor-infiltrating immune cells in gastrointestinal cancers. ROMO1 is closely related to the inner mitochondrial membrane proteins (TIMM) family. The study revealed that ROMO1 is of significant clinical importance for gastrointestinal cancers and may have potential clinical utility in treatment and prognosis. Functional tests on cell lines derived from these particular gastrointestinal cancers can also be performed in vitro to evaluate the impact of the ROMO1 gene and other factors, like potential drugs, on the expression of these genes and the development and progression of the cancer.Öğe Determination of FGFR1 Functions in Cytarabine Treatment of Acute Myeloid Leukemia Through Bioinformatics Analysis(Bentham Science Publ Ltd, 2024) Misir, Sema; Yaman, Serap Ozer; Aykac, Okan; Akidan, Osman; Merde, Irem Bozbey; Hepokur, CeylanAim Among the most prevalent subtypes of acute leukemia is acute myeloid leukemia (LAML). Consequently, it is essential to understand the molecular causes of LAML and find its predictive and diagnostic biomarkers. The aim of this study is to determine the molecular functions of fibroblast growth factor receptor 1(FGFR1) involved in LAML pathogenesis and its potential therapeutic effect for AML treatment.Methods The molecular docking interaction of the Cytarabine with its target FGFR1 was examined. The Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2), and UALCAN tools database were used to obtain the LAML gene expression datasets. Gene functional annotation was performed to investigate the DEGs' possible role. Using the Interactive Gene database retrieval tool (STRING) and a few chosen hub modules from the GeneMANIA database, the protein-protein interaction (PPI) network were constructed. A survival analysis was performed on the effects of hub genes on the overall survival of LAML patients.Results As a result of docking, a strong interaction was observed between cytarabine and FGFR1. It has been discovered that cytarabine can reverse FGFR1 expression. The survival study results showed an association between the prognosis of AML patients and one of the central genes, FGFR1.Conclusion The expression profile and functions of FGFR1 were determined in LAML patients. It has been shown that FGFR1 can be a viable therapeutic target for LAML and a possible biomarker for diagnosis.Öğe Identification of a Novel hsa_circ_0058058/miR-324-5p Axis and Prognostic/Predictive Molecules for Acute Myeloid Leukemia Outcome by Bioinformatics-Based Analysis(Mdpi, 2024) Misir, Sema; Ozer Yaman, Serap; Petrovic, Nina; Sami, Ahmad; Akidan, Osman; Hepokur, Ceylan; Aliyazicioglu, YukselSimple Summary Acute myeloid leukemia (LAML) is among the most common types of hematological cancer. In recent years, it has been shown that circular RNA (circRNA) and microRNA (miRNA) can be used as markers for diagnosis and treatment results in tumor development, in the early stages of the tumor or after chemotherapy. This study aimed to identify the disease-related circRNA-miRNA-mRNA network by bioinformatic analysis and investigate the mechanisms in the development and progression of LAML. Bioinformatics analyses identified the hsa_circ_0058058/miR-324-5p axis in LAML and its possible functions in LAML development. It was found that hsa_circ_0058058 could regulate the expression of AP1G1 and SP1 through miR-324-5p to promote angiogenesis, cell cycle, and DNA replication processes. Downregulation of Hsa circ-0058058 may contribute to the anticancer functions of miR-324-5p on LAML tumorigenesis. Upregulation of miR-324-5p could abolish the oncogenic effects of AP1G1 and SP1 on LAML tumorigenesis.These analyses demonstrated their important role by showing that these molecules can be used as a diagnostic biomarker and therapeutic target for the treatment of LAML.Abstract Acute myeloid leukemia (LAML) is one of the most prevalent hematological malignancies. In recent years, while targeted approaches have shown promise in the fight against cancer, the treatability and prognosis of patients remain inadequate due to the shortage of drugs. Noncoding RNAs, especially circular RNA (circRNA) and microRNA (miRNA), have been shown to play a unique role in tumor development. This study aims to identify the disease-associated circRNA-miRNA-mRNA network by bioinformatic analysis and investigate the mechanisms in the development and progression of LAML. Additionally, it reveals the promising roles of these molecules as a diagnostic biomarker and therapeutic target for LAML treatment. Using various bioinformatics approaches, we identified the hsa_circ_0058058/miR-324-5p axis in LAML and its possible functions in LAML development. According to our results, hsa circ-0058058 can regulate the expression of AP1G1 and SP1 through miR-324-5p to support angiogenesis, the cell cycle, and DNA replication processes. Downregulation of hsa circ-0058058 may contribute to the anticancer functions of miR-324-5p on LAML tumorigenesis, and upregulation of miR-324-5p can abolish the oncogenic effects of AP1G1 and SP1 on LAML tumorigenesis. Additionally, highly enriched pathways indicated possible interactions between molecules underlying LAML pathology. Targeted molecules within this network may be able to function as therapeutic and diagnostic biomarkers for disease, while more research and clinical confirmation are needed.Öğe mir-188-5p emerges as an oncomir to promote chronic myeloid leukemia via upregulation of BUB3 and SUMO2(Springer, 2025) Akidan, Osman; Petrovic, Nina; Misir, SemaBackgroundChronic myeloid leukemia (CML) is an aggressive malignancy originating from hematopoietic stem cells. miRNAs play a role in physiological and developmental processes, including cellular proliferation, apoptosis, angiogenesis, and differentiation, and in CML's prognosis, diagnosis, and treatment. This study aimed to investigate the function and possible mechanisms of action of miR-188-5p in the development and progression of chronic myeloid leukemia.Methods and resultsmiRNA expression profiles were obtained from the GSE90773 dataset in the Gene Expression Omnibus (GEO). GEO2R was used to identify differentially expressed miRNAs. miRNET, miRDB, CancerSEA, GeneMANIA, and BioGRID databases were applied to assess the biological function of miRNA and target molecules in CML. RT-PCR performed validation analyses of miRNA and target molecules in CML. To determine the power of miR-188-5p expression levels to distinguish patients with CML from control, the ROC analysis was performed. miR-188-5p is significantly increased in K-562 cells, and overexpression of miR-188-5p was associated with clinicopathological features. miR-188-5p showed significantly higher AUC values (AUC = 1.0, p = 0.0001). The cut-off of miR-188-5p was 6.74. miRDB and mirNET predicted BUB3 and SUMO2 as a potential target gene of miR-188-5p. Additionally, increased expression of BUB3 and SUMO2 was observed in the K-562 cell. Bub3 is implicated in apoptosis and the cell cycle, whereas Sumo2 protein sumoylation and DNA binding are believed to contribute to catabolic processes.ConclusionsOur results suggest that miR-188-5p acts as an oncomiRNA in CML pathogenesis and may be a promising therapeutic target for CML.