title: Preliminary Analysis of the Expression of Selected Proangiogenic and Antioxidant Genes and MicroRNAs in Patients with Non-Muscle-Invasive Bladder Cancer.
abstract: Heme oxygenase-1 (HO-1) is an enzyme contributing to the development and progression of different cancer types. HO-1 plays a role in pathological angiogenesis in bladder cancer and contributes to the resistance of this cancer to therapy. It also regulates the expression of microRNAs in rhabdomyosarcoma and non-small cell lung cancer. The expression of HO-1 may be regulated by hypoxia inducible factors (HIFs) and Nrf2 transcription factor. The expression of HO-1 has not so far been examined in relation to Nrf2, HIF-1α, and potential mediators of angiogenesis in human bladder cancer. We measured the concentration of proinflammatory and proangiogenic cytokines and the expression of cytoprotective and proangiogenic mRNAs and miRNAs in healthy subjects and patients with bladder cancer. HO-1 expression was upregulated together with HIF-1α, HIF-2α, and Nrf2 in bladder cancer in comparison to healthy tissue. VEGF was elevated both at mRNA and protein level in the tumor and in sera, respectively. Additionally, IL-6 and IL-8 were increased in sera of patients affected with urothelial bladder cancer. Moreover, miR-155 was downregulated whereas miR-200c was elevated in cancer biopsies in comparison to healthy tissue. The results indicate that the increased expression of HO-1 in bladder cancer is paralleled by changes in the expression of other potentially interacting genes, like Nrf2, HIF-1α, HIF-2α, IL-6, IL-8, and VEGF. Further studies are necessary to also elucidate the potential links with miR-155 and miR-200c.
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland. m.kozakowska@uj.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kozakowska
authors.affiliation: Department of Pediatric Urology, Jagiellonian University Medical College, 30-688 Krakow, Poland. bdobrowolska@o2.pl.|Department and Clinic of Urology, Jagiellonian University Medical College, 31-530 Krakow, Poland. bdobrowolska@o2.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dobrowolska-Glazar
authors.affiliation: Department of Pathomorphology, Jagiellonian University Medical College, 31-531 Krakow, Poland. k.okon@uj.edu.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Okoń
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland. alicja.jozkowicz@uj.edu.pl.
authors.forename: Alicja
authors.initials: A
authors.lastname: Józkowicz
authors.affiliation: Department and Clinic of Urology, Jagiellonian University Medical College, 31-530 Krakow, Poland. zdobrowol@su.krakow.pl.|Department of Urology, University of Rzeszow, 35-959 Rzeszow, Poland. zdobrowol@su.krakow.pl.
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Dobrowolski
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland. jozef.dulak@uj.edu.pl.|Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Krakow, Poland. jozef.dulak@uj.edu.pl.
authors.forename: Józef
authors.initials: J
authors.lastname: Dulak
keywords: Nrf2; VEGF; angiogenesis; bladder cancer; heme oxygenase-1; hypoxia inducible factor; miR-155; miR-200c; urothelial cancer