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Updated: Feb 14, 2026

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
Post-Transcriptional Control of Angiotensin II Type 1 Receptor Regulates Osteosarcoma Cell Death
Yue Zhao1, Kaicheng Xu2, Peng Liu3
1Department of Vascular Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.
Background/Aims:
MicroRNAs (miRNAs) play an essential role in the tumorigenesis of osteosarcoma (OS). However, the effects of miR-1248 on chemo-resistant potential of OS have not been studied. Here, we addressed this question.
Methods:
The levels of miR-1248 and apoptotic protein angiotensin II type 1 receptor (AGTR1) in OS specimens were examined by RT-qPCR and Western blotting, respectively. The relationship between miR-1248 and AGTR1 was determined by analysis of Spearman's Rank Correlation Coefficients. The patient survival was determined with Kaplan-Meier curves. Bioinformatics analyses were done to predict microRNAs (miRNAs) that target AGTR1. The functional binding of miRNAs to AGTR1 mRNA was examined by a dual luciferase reporter assay. Cell viability was determined by an CCK-8 assay. Apoptosis was determined by a fluorescence-based apoptosis assay.
Results:
The levels of miR-1248 were significantly elevated while the levels of AGTR1 were significantly decreased in OS specimens than in paired adjacent normal tissue. The levels of miR-1248 were negatively correlated to the levels of AGTR1. Moreover, the patients with high miR-1248 levels had poorer survival than those with low MiR-1248 levels, and the patients with low AGTR1 levels had poorer survival than those with high AGTR1 levels. MiR-1248 inhibited protein translation of AGTR1, through binding to the 3'-UTR of the AGTR1 mRNA. The AGTR1-mediated cell apoptosis was suppressed by overexpressing miR-1248, and was augmented by depleting miR-1248.
Conclusion:
Increased miR-1248 expression in OS may inhibit AGTR1-mediated cancer cell death in chemotherapy. The outcome of chemotherapy may be improved by the suppression of miR-1248 in OS cells.
Insights
MicroRNA-1248 (miR-1248) is elevated in osteosarcoma (OS) and reduces chemotherapy effectiveness by inhibiting AGTR1, suggesting miR-1248 suppression could improve patient outcomes.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are crucial in osteosarcoma (OS) tumorigenesis.
- The role of miR-1248 in OS chemoresistance remains uninvestigated.
Purpose of the Study:
- To investigate the effect of miR-1248 on the chemo-resistant potential of osteosarcoma.
- To explore the relationship between miR-1248 and angiotensin II type 1 receptor (AGTR1) in OS.
Main Methods:
- Quantified miR-1248 and AGTR1 levels in OS tissues using RT-qPCR and Western blotting.
- Assessed the correlation between miR-1248 and AGTR1, and patient survival.
- Utilized bioinformatics, dual luciferase reporter assays, CCK-8, and apoptosis assays to determine functional interactions.
Main Results:
- miR-1248 was upregulated, while AGTR1 was downregulated in OS tissues.
- High miR-1248 and low AGTR1 levels correlated with poorer patient survival.
- miR-1248 directly inhibited AGTR1 translation and suppressed AGTR1-mediated apoptosis.
Conclusions:
- Increased miR-1248 expression in OS may reduce chemotherapy efficacy by inhibiting AGTR1-mediated cell death.
- Suppression of miR-1248 in OS cells could potentially enhance chemotherapy outcomes.
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