Cell-type specific effects of the long non-coding RNA HIF1A-AS3 on HIF1A expression in kidney cells
Abstract The hypoxia-inducible factor 1α (Hif1α) represents the master transcription factor coordinating cellular responses to oxygen depletion. With hundreds of target genes it plays a key role in numerous bio-medical conditions as well as neoplastic and non-cancerous diseases, which in turn requir...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-12441-5 |
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| Summary: | Abstract The hypoxia-inducible factor 1α (Hif1α) represents the master transcription factor coordinating cellular responses to oxygen depletion. With hundreds of target genes it plays a key role in numerous bio-medical conditions as well as neoplastic and non-cancerous diseases, which in turn requires a strict regulation. Long non-coding RNAs have the potential to virtually control every step of gene expression. We aimed to investigate the expression and role of HIF1A antisense lncRNAs HIF1A-AS1, AS2, and AS3 under hyperglycemic, hypoxic, or both conditions in three non-cancerous human renal cell types: HK-2 cells, primary RPTECs, and mesangial cells. We observed that HIF1A-AS2 and AS3 expression was upregulated under oxygen deprivation. Furthermore, knockdown (KD) of HIF1A-AS3 resulted in a significant reduction of HIF1A-AS2 and even more important of Hif1α in HK-2 cells but not mesangial cells. While KD of HIF1A also had a diminishing effect on HIF1A-AS2 and AS3 RNA levels, KD of HIF1A-AS2 only affected HIF1A-AS3 but not HIF1A. Treating HK-2 cells with Actinomycin D revealed a high HIF1A-AS3 RNA stability. In conclusion, our data reveal a cell-type specific effect of HIF1A-AS3 on HIF1A RNA and protein expression which might allow the development of a cell-type specific HIF1A antagonist based on lncRNAs. |
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| ISSN: | 2045-2322 |