Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Seles, M.
Identification and characterisation of long non-coding RNA PANTR1 in clear-cell renal cell carcinoma
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medical University of Graz; 2021. pp. 101
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- Autor*innen der Med Uni Graz:
- Seles Maximilian
- Betreuer*innen:
- Hutterer Georg
- Pichler Martin
- Zigeuner Richard
- Altmetrics:
- Abstract:
- Non-coding RNAs (ncRNAs), notably long non-coding RNAs (lncRNA), have recently been under intensive investigation for their role in carcinogenesis. POU3F3 adjacent non-coding transcript 1 (PANTR1) is a lncRNA with remarkable expression during foetal brain and renal development. Besides, it is known for a versatile role during carcinogenesis of different types of cancer. No available information exists about its role and a possible mode of action in clear-cell renal cell carcinoma (ccRCC). In-silico data analysis of publicly available databases revealed PANTR1 expression to be confined to corresponding and healthy foetal and adult and cancerous human brain and kidney tissue. Moreover, it was significantly up-regulated in ccRCC compared to matched non-cancerous kidney tissue (p<0.001). PANTR1 expression was not associated with altered overall survival (OS) in these publicly available cohorts. An siRNA-mediated knockdown approach in three different ccRCC cell lines demonstrated significant differences in cellular growth also by induction of apoptosis. We could further demonstrate significant differences in expression of angiogenic genes including the vascular endothelial growth factor-A (VEGF-A) by qRT-PCR. By use of publicly available datasets, VEGF-A and PANTR1 showed a significant correlation (p=3.1x10-11, R=0.28, Spearman’s rank correlation coefficient). Using an in vitro angiogenesis assay, knockdown of PANTR1 in human umbilical vein endothelial cells (HUVECs) was established as a surrogate marker for angiogenesis. Several vascularisation patterns and endothelial cell migration were significantly reduced in PANTR1- knockdown cells compared to normal HUVECs. LncRNA PANTR1 seems to be an oncogenic driver for ccRCC carcinogenesis with a promising potential as a future therapeutic target.