PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 4Citation - Scopus: 7Master Regulators of Posttranscriptional Gene Expression Are Subject To Regulation(Humana Press, 2014) Hamid, Syed Muhammad; Akgül, BünyaminMicroRNAs (miRNAs) are small noncoding RNAs of 17-25 nt in length that control gene expression posttranscriptionally. As master regulators of posttranscriptional gene expression, miRNAs themselves are subject to tight regulation at multiple steps. The most common mechanisms include miRNA transcription, processing, and localization. Additionally, intricate feedback loops between miRNAs and transcription factors result in unidirectional, reciprocal, or self-directed elegant control mechanisms. In this chapter, we focus on the posttranscriptional regulatory mechanisms that generate miRNAs whose sequence might be slightly different from the miRNA-coding sequences. Hopefully, this information will be helpful in the discovery of novel miRNAs as well as in the analysis of deep-sequencing data and ab initio prediction of miRNAs. © Springer Science+Business Media New York 2014.Article Citation - WoS: 44Citation - Scopus: 42Inflammation-Mediated Abrogation of Androgen Signaling: an in Vitro Model of Prostate Cell Inflammation(John Wiley and Sons Inc., 2014) Debeleç Bütüner, Bilge; Alapınar, Cansu; Varışlı, Lokman; Erbaykent Tepedelen, Burcu; Hamid, Syed Muhammad; Gönen Korkmaz, Ceren; Korkmaz, Kemal SamiAs a link between inflammation and cancer has been reported in many studies, we established an in vitro model of prostatic inflammation to investigate the loss of androgen receptor (AR)-mediated signaling in androgen responsive prostate cell lines. First, the U937 monocyte cell line was differentiated into macrophages using phorbol acetate (PMA), and cells were induced with lipopolysaccharide (LPS) for cytokine secretion. Next, the cytokine levels (TNFα, IL-6, and IL1β) in conditioned media (CM) were analyzed. Prostate cells were then fed with CM containing varying concentrations of TNFα, and IkB degradation, nuclear factor kappa B (NFκB) translocation and transactivation, and the expression of matrix metalloproteinase-8 (MMP8) and matrix metalloproteinase-9 (MMP9) were then assessed. As a result of CM treatment, ubiquitin-mediated AR degradation, which was restored using anti-TNFα antibody neutralization, led to both a decrease in KLK4, PSA, and NKX3.1 expression levels and the upregulation of GPX2. In addition to the loss of AR, acute and chronic CM exposure resulted in p53 degradation and consequent p21 downregulation, which was also restored by either androgen administration or ectopic NKX3.1 expression via the stabilization of MDM2 levels in LNCaP cells. Additionally, CM treatment enhanced H2AX(S139) phosphorylation (a hallmark of DNA damage) and genetic heterogeneity in the absence of androgens in prostate cells without activating mitochondrial apoptosis. Thus, the data suggest that inflammatory cytokine exposure results in the loss of AR and p53 signaling in prostate cells and facilitates genetic heterogeneity via ROS accumulation to promote prostate carcinogenesis.Article Citation - WoS: 12Citation - Scopus: 12Decreased Expression of Efs Is Correlated With the Advanced Prostate Cancer(SAGE Publications Inc., 2015) Sertkaya, Selda; Hamid, Syed Muhammad; Dilsiz, Nihat; Varışlı, LokmanProstate cancer is the most frequently diagnosed malignant neoplasm in men in the developed countries. Although the progression of prostate cancer and the processes of invasion and metastasis by tumor cells are comparatively well understood, the genes involved in these processes are not fully determined. Therefore, a common area of research interest is the identification of novel molecules that are involved in these processes. In the present study, we have used in silico and experimental approaches to compare the expression of embryonal Fyn-associated substrate (EFS) between normal prostate and prostate cancer. We showed that EFS expression is remarkably downregulated in prostate cancer cells, compared to normal prostate cells. We also found that decreased expression of EFS in prostate cancer cells is due to DNA methylation. In addition, we showed that high EFS expression is important to suppress a malignant behavior of prostate cancer cells. Therefore, we suggest that EFS should be considered as a novel tumor suppressor gene in prostate cancer.Article Citation - WoS: 8Citation - Scopus: 8Nkx3.1 Contributes To S Phase Entry and Regulates Dna Damage Response (ddr) in Prostate Cancer Cell Lines(Academic Press Inc., 2011) Erbaykent Tepedelen, Burcu; Özmen, Besra; Varışlı, Lokman; Gönen Korkmaz, Ceren; Debeleç Bütüner, Bilge; Hamid, Syed Muhammad; Çakmak, Özgür Yılmazer; Korkmaz, Kemal SamiNKX3.1 is an androgen-regulated homeobox gene that encodes a tissue-restricted transcription factor, which plays an important role in the differentiation of the prostate epithelium. Thus, the role of NKX3.1 as a functional topoisomerase I activity enhancer in cell cycle regulation and the DNA damage response (DDR) was explored in prostate cancer cell lines. As an early response to DNA damage following CPT-11 treatment, we found that there was an increase in the γH2AX (S139) foci number and that total phosphorylation levels were reduced in PC-3 cells following ectopic NKX3.1 expression as well as in LNCaP cells following androgen administration. Furthermore, upon drug treatment, the increase in ATM (S1981) phosphorylation was reduced in the presence of NKX3.1 expression, whereas DNA-PKcs expression was increased. Additionally, phosphorylation of CHK2 (T68) and NBS1 (S343) was abrogated by ectopic NKX3.1 expression, compared with the increasing levels in control PC-3 cells in a time-course experiment. Finally, NKX3.1 expression maintained a high cyclin D1 expression level regardless of drug treatment, while total γH2AX (S139) phosphorylation remained depleted in PC-3, as well as in LNCaP, cells. Thus, we suggest that androgen regulated NKX3.1 maintains an active DDR at the intra S progression and contributes to the chemotherapeutic resistance of prostate cancer cells to DNA damaging compounds.