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Updated: Apr 21, 2026
Quantitative Real-Time PCR Evaluation of microRNA Expressions in Mouse Kidney with Unilateral Ureteral Obstruction
Published on: August 27, 2020
Distinct microRNA expression profiles in mouse renal cortical tissue after 177Lu-octreotate administration
Emil Schüler1, Toshima Z Parris2, Khalil Helou2
1Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Aim:
The aim of this study was to investigate the variation of the miRNA expression levels in normal renal cortical tissue after 177Lu-octreotate administration, a radiopharmaceutical used for treatment of neuroendocrine cancers.
Methods:
Female BALB/c nude mice were i.v. injected with 1.3, 3.6, 14, 45, or 140 MBq 177Lu-octreotate, while control animals received saline. The animals were killed at 24 h after injection and total RNA, including miRNA, was extracted from the renal cortical tissue and hybridized to the Mouse miRNA Oligo chip 4plex to identify differentially regulated miRNAs between exposed and control samples.
Results:
In total, 57 specific miRNAs were differentially regulated in the exposed renal cortical tissues with 1, 29, 21, 27, and 31 miRNAs identified per dose-level (0.13, 0.34, 1.3, 4.3, and 13 Gy, respectively). No miRNAs were commonly regulated at all dose levels. miR-194, miR-107, miR-3090, and miR-3077 were commonly regulated at 0.34, 1.3, 4.3, and 13 Gy. Strong effects on cellular mechanisms ranging from immune response to p53 signaling and cancer-related pathways were observed at the highest absorbed dose. Thirty-nine of the 57 differentially regulated miRNAs identified in the present study have previously been associated with response to ionizing radiation, indicating common radiation responsive pathways.
Conclusion:
In conclusion, the 177Lu-octreotate associated miRNA signatures were generally dose-specific, thereby illustrating transcriptional regulation of radiation responsive miRNAs. Taken together, these results imply the importance of miRNAs in early immunological responses in the kidneys following 177Lu-octreotate administration.
Insights
This study investigated microRNA (miRNA) expression in kidney tissue after 177Lu-octreotate treatment for neuroendocrine cancers. Results show dose-specific miRNA changes, suggesting their role in early kidney immune responses to radiation.
Area of Science:
- Oncology
- Radiopharmaceuticals
- Molecular Biology
Background:
- 177Lu-octreotate is a radiopharmaceutical used for neuroendocrine cancer treatment.
- Understanding its effects on normal tissues, like the kidney, is crucial for patient safety.
- MicroRNAs (miRNAs) are key regulators of gene expression and can be affected by radiation.
Purpose of the Study:
- To investigate changes in miRNA expression in normal renal cortical tissue following 177Lu-octreotate administration.
- To identify specific miRNAs that are differentially regulated in response to varying doses of 177Lu-octreotate.
- To explore the functional implications of these miRNA changes in kidney tissue.
Main Methods:
- Female BALB/c nude mice were administered different doses of 177Lu-octreotate or saline (control).
- Renal cortical tissue was collected 24 hours post-injection.
- Total RNA and miRNA were extracted and analyzed using a Mouse miRNA Oligo chip to identify differentially expressed miRNAs.
Main Results:
- 57 specific miRNAs were found to be differentially regulated in kidney tissue across different radiation doses.
- MiRNA regulation was generally dose-specific, with some miRNAs commonly regulated at higher doses.
- Thirty-nine of the regulated miRNAs are known to be associated with response to ionizing radiation, indicating conserved radiation-responsive pathways.
- Significant effects on cellular mechanisms, including immune response and p53 signaling, were observed at the highest dose.
Conclusions:
- 177Lu-octreotate administration leads to dose-specific miRNA expression signatures in renal tissue.
- These findings highlight the transcriptional regulation of radiation-responsive miRNAs.
- The results suggest that miRNAs play a significant role in early immunological responses within the kidneys after 177Lu-octreotate treatment.
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