Investigating miRNA-related Pathways Contributing to Kidney Cancer Pathogenesis.

Anticancer Res

Department of Laboratory Medicine, and the Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada;

Published: May 2022

Background/aim: Renal cell carcinoma is one of the most common types of cancer worldwide. Understanding tumor pathogenesis is important in developing better treatment. Micro RNAs (miRNAs) are key players in controlling cancer behavior. Transcription factors (TFs) are potentially responsible for controlling miRNA expression and dysregulation in kidney cancer. The objective of this study was to better understand the TF-miRNA axis of interaction.

Materials And Methods: We utilized publicly available databases to investigate miRNA-TF interactions, including ChipBase database for TFs that binds to the promoters of miRNAs which are dysregulated in renal cell carcinoma. Renal cancer-specific TFs were extracted from the list using the GENT Database. We assessed the prognostic significance of these TFs using cBioPortal.

Results: We identified TFs which bind to miRNA promoters, including hepatocyte nuclear factor-4 alpha (HNF-4α), E2F transcription factor 4 (E2F4), signal transducer and activator of transcription 1 (STAT1), Sp1 transcription factor (SP1), GATA binding protein 6 (GATA6), and nuclear factor kappa B (NFκB). These TFs were positively correlated with their targeted miRNAs, including miR-200c, miR-15a, miR-146b, miR-155, and miR-223. We recognized unique patterns of interactions, including a divergent effect in which multiple miRNAs are simultaneously affected by the same TF.

Conclusion: Our results show that miRNA-TF interaction is complex. Expression levels of these TFs were found to correlate with renal carcinoma prognosis and have potential utility as biomarkers for aggressive tumor behavior. Targeting these TFs may result in modulating the expression of their target genes and miRNAs, with subsequent therapeutic implications.

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15714DOI Listing

Publication Analysis

Top Keywords

kidney cancer
8
renal cell
8
cell carcinoma
8
tfs
8
interactions including
8
transcription factor
8
mirnas
5
investigating mirna-related
4
mirna-related pathways
4
pathways contributing
4

Similar Publications

Cardiovascular-kidney-metabolic (CKM) syndrome is the association between obesity, diabetes, CKD (chronic kidney disease), and cardiovascular disease. GDF-15 mainly acts through the GFRAL (Glial cell line-derived neurotrophic factor Family Receptor Alpha-Like) receptor. GDF-15 and GDFRAL complex act mainly through RET co-receptors, further activating Ras and phosphatidylinositol-3-kinase (PI3K)/Akt pathways through downstream signaling.

View Article and Find Full Text PDF

Doublecortin-like kinase 1 (DCLK1) has been revealed to be involved in modulating cancer stemness and tumor progression, but its role in prostate cancer (PCa) remains obscure. Castration-resistant and metastatic PCa exhibit aggressive behaviors, and current therapeutic approaches have shown limited beneficial effects on the overall survival rate of patients with advanced PCa. This study aimed to investigate the biological role and potential molecular mechanism of DCLK1 in the progression of PCa.

View Article and Find Full Text PDF

Carcinogenesis often involves significant alterations in the cancer genome, marked by large structural variants (SVs) and copy number variations (CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping (OGM) and nanopore sequencing [Oxford Nanopore Technologies (ONT)] bridge this resolution gap and offer enhanced performance for cytogenetic applications.

View Article and Find Full Text PDF

Background: Damage to brain white matter often occurs in individuals with chronic kidney disease, which might be related to their cognitive decline. This study aims to investigate tract-specific white matter damage in patients with end-stage kidney disease by using fixel-based analysis.

Methods: Images of 31 end-stage kidney disease patients and 16 normal controls (aged: 61.

View Article and Find Full Text PDF

The positive feedback loop between SP1 and MAP2K2 significantly drives resistance to VEGFR inhibitors in clear cell renal cell carcinoma.

Int J Biol Sci

January 2025

Department of Urology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.

Clear cell renal cell carcinoma (ccRCC) is one of the most common and aggressive malignancies of the urinary system. Despite being the first-line treatment for advanced ccRCC, vascular endothelial growth factor receptor inhibitors (VEGFRis) face significant limitations due to both initial and acquired resistance, which impede complete tumor eradication. Using a CRISPR/Cas9 library screening approach, was identified as a resistance-associated gene for three prevalent VEGFRis (Sunitinib, Axitinib, and Sorafenib).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!