Axl RTK and microRNAs in urogenital cancers
type: CreativeWork
description: This thesis is based on four projects focused on the Axl receptor tyrosine kinase (RTK) and microRNAs in clear cell renal cell carcinoma (ccRCC) and in prostate cancer (PCa). Paper I focuses on differentially expressed microRNAs in ccRCC. We used bioinformatics methods to identify candidate microRNAs in a publically available cohort of ccRCC, which were measured in a cohort of 198 RCC tumors. Importantly, we identified a 2-microRNA ratio, miR(21/10b), which is an independent prognostic factor in metastasis-free ccRCC patients. These microRNAs are both linked to chronic kidney disease, a risk factor for ccRCC, and could potentially be involved in the progression from kidney disease to renal cancer. In Paper II, our aim was to elucidate if members of the miR-34 family, which is a family of microRNA tumor suppressors, could regulate Axl in ccRCC, and also to determine miR-34a/b/c expression in ccRCC tumors, as reports have been conflicting. Axl has previously been shown to be a target of miR-34a in solid cancers, and high Axl expression correlates with worsened prognosis in RCC. We showed that both miR-34a and miR-34c are direct regulators of Axl in vitro, however miR-34a expression is increased in ccRCC and does not correlate with Axl mRNA or protein in ccRCC tumors, and has no correlation with survival in ccRCC. Paper III was aimed at elucidating whether any of the miR-34 family members could regulate Axl expression PCa, as both miR-34a and miR-34c are downregulated in PCa, and Axl expression is increased in PCa and correlates with disease severity. In addition, we sought to elucidate the role of decreased Axl expression in miR-34a/c-mediated tumor suppression. Although we could show direct regulation of Axl by miR-34a and miR-34c, our results did not support regulation of Axl as the main function in miR-34a/c tumor suppression in PCa. The main functional outcome of miR-34a/c-mediated loss of Axl seemed to be in reduced proliferation in response to Gas6. Finally, pap…
abstract: This thesis is based on four projects focused on the Axl receptor tyrosine kinase (RTK) and microRNAs in clear cell renal cell carcinoma (ccRCC) and in prostate cancer (PCa). Paper I focuses on differentially expressed microRNAs in ccRCC. We used bioinformatics methods to identify candidate microRNAs in a publically available cohort of ccRCC, which were measured in a cohort of 198 RCC tumors. Importantly, we identified a 2-microRNA ratio, miR(21/10b), which is an independent prognostic factor in metastasis-free ccRCC patients. These microRNAs are both linked to chronic kidney disease, a risk factor for ccRCC, and could potentially be involved in the progression from kidney disease to renal cancer. In Paper II, our aim was to elucidate if members of the miR-34 family, which is a family of microRNA tumor suppressors, could regulate Axl in ccRCC, and also to determine miR-34a/b/c expression in ccRCC tumors, as reports have been conflicting. Axl has previously been shown to be a target of miR-34a in solid cancers, and high Axl expression correlates with worsened prognosis in RCC. We showed that both miR-34a and miR-34c are direct regulators of Axl in vitro, however miR-34a expression is increased in ccRCC and does not correlate with Axl mRNA or protein in ccRCC tumors, and has no correlation with survival in ccRCC. Paper III was aimed at elucidating whether any of the miR-34 family members could regulate Axl expression PCa, as both miR-34a and miR-34c are downregulated in PCa, and Axl expression is increased in PCa and correlates with disease severity. In addition, we sought to elucidate the role of decreased Axl expression in miR-34a/c-mediated tumor suppression. Although we could show direct regulation of Axl by miR-34a and miR-34c, our results did not support regulation of Axl as the main function in miR-34a/c tumor suppression in PCa. The main functional outcome of miR-34a/c-mediated loss of Axl seemed to be in reduced proliferation in response to Gas6. Finally, pap…
author: Fritz, Helena
language: eng
keywords: Medicinal Chemistry
date published: 2015
date modified: 2026-07-24T02:59:36Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Translational Medicine