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Updated: May 26, 2025
Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
'Investigation of miRNAs That Affect the PI3K/AKT/mTOR Signaling Pathway in Endometrial Cancer'
Hasan Öz1, Necmiye Canacankatan2, Şerife Efsun Antmen1
1Department of Biochemistry, Faculty of Pharmacy, Mersin University, Mersin, Turkey.
Abstract:
Endometrial cancer is a prevalent type of cancer among women worldwide. The irregularity of the PI3K/AKT/mTOR signaling pathway plays a role in the pathogenesis of many cancer types. MicroRNAs are small noncoding RNAs that play crucial roles in the pathogenesis of different cancer types. MicroRNAs target many key components of the PI3K/AKT/mTOR pathway in human tumors. In this study the PI3K/AKT/mTOR pathway was affected in endometrial cancer, and the expression levels of miR-7, miR-17, miR-145, miR-155, miR-206, miR-221, miR-222 were determined. In addition, in silico analyses were examine the molecular interactions between miRNAs and target genes. Identifying dysregulated miRNA expression in endometrial cancer is important for developing miRNA-based therapeutic strategies. In our study, Grade 1 (n = 16), Grade 2 (n = 16), Grade 3 (n = 16), tissues diagnosed with endometrioid adeno carcinoma, control 1 (n = 16) secretory phase and control 2 (n = 16) proliferative phase healthy endometrial tissues without endometrial cancer were included. miRNA expression analysis was performed using the real-time PCR. In our study, the expression of miR-7-5p, miR-145-5p, and miR-206 decreased, whereas the expression of miR-17-5p, miR-221-3p, and miR-222-3p increased in endometrial cancer (p < 0,05). Statistically significant results were not obtained to for the expression levels of miR-21-5p and miR-155-5p. miR-7-5p targets PIK3CD, PIK3R3, PIK3CB and AKT3, miR-17-5p targets PIK3R1 and AKT3, miR-21-5p target PIK3R1, miR-145-5p target AKT3, miR-155-5p targets PIK3CA and PIK3R1, miR-206 target PIK3C2A, miR-221-3p and miR-222-3p target PIK3R1 as identified via in silico analysis. These results can shed light on the development of molecular-targeted therapy strategies. Treatment strategies can be developed by designing ASOs, LNAs, miRNA antagomirs, or miRNA sponges for upregulated miR-17-5p, miR-221-3p, and miR-222-3p, and miRNA mimics for downregulated miR-7-5p, miR-145-5p, and miR-206.
Insights
This study investigated microRNA (miRNA) expression in endometrial cancer, finding specific miRNAs are dysregulated in the PI3K/AKT/mTOR pathway. These findings could lead to new targeted therapies for endometrial cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Endometrial cancer is a common gynecological malignancy.
- The PI3K/AKT/mTOR signaling pathway is frequently dysregulated in various cancers, including endometrial cancer.
- MicroRNAs (miRNAs) are key regulators of gene expression and play critical roles in cancer development.
Purpose of the Study:
- To investigate the expression levels of specific miRNAs targeting the PI3K/AKT/mTOR pathway in endometrial cancer tissues.
- To analyze the molecular interactions between dysregulated miRNAs and their target genes within the PI3K/AKT/mTOR pathway.
- To identify potential miRNA-based therapeutic targets for endometrial cancer.
Main Methods:
- Real-time PCR was used to quantify miRNA expression levels in endometrial cancer tissues (Grades 1-3) and healthy endometrial tissues (secretory and proliferative phases).
- In silico analyses were performed to predict and examine the interactions between miRNAs and their target genes.
- Patient tissues were categorized into different grades of endometrioid adenocarcinoma and healthy controls.
Main Results:
- Downregulation of miR-7-5p, miR-145-5p, and miR-206 was observed in endometrial cancer tissues (p < 0.05).
- Upregulation of miR-17-5p, miR-221-3p, and miR-222-3p was detected in endometrial cancer tissues (p < 0.05).
- No statistically significant changes in miR-21-5p and miR-155-5p expression were found.
Conclusions:
- Specific miRNAs (miR-7-5p, miR-145-5p, miR-206, miR-17-5p, miR-221-3p, miR-222-3p) are significantly dysregulated in endometrial cancer.
- These dysregulated miRNAs target key components of the PI3K/AKT/mTOR pathway, suggesting their involvement in endometrial cancer pathogenesis.
- The identified miRNA signatures offer potential for developing novel molecular-targeted therapies, such as miRNA mimics or antagomirs, for endometrial cancer treatment.
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