Targeting the mTOR Signaling Pathway Through miR‐100 and miR‐101 in De Novo Acute Myeloid Leukemia: Implications for Therapeutic Intervention

ABSTRACT Background Microribonucleic acid (MicroRNAs/miRNAs) play a significant role in cancer progression by changing cellular functions through the modulation of protein expressions. The potential of different miRNAs to alter the expression of the mammalian target of rapamycin (mTOR)/protein kinas...

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Main Authors: Maryam Kargar, Mehdi Allahbakhshian Farsani, Javad Garavand, Mahnaz Gorji, Mohammad Rafiee, Seyed Sobhan Bahreiny, Mohammad Hossein Mohammadi
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Cancer Reports
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Online Access:https://doi.org/10.1002/cnr2.70264
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author Maryam Kargar
Mehdi Allahbakhshian Farsani
Javad Garavand
Mahnaz Gorji
Mohammad Rafiee
Seyed Sobhan Bahreiny
Mohammad Hossein Mohammadi
author_facet Maryam Kargar
Mehdi Allahbakhshian Farsani
Javad Garavand
Mahnaz Gorji
Mohammad Rafiee
Seyed Sobhan Bahreiny
Mohammad Hossein Mohammadi
author_sort Maryam Kargar
collection DOAJ
description ABSTRACT Background Microribonucleic acid (MicroRNAs/miRNAs) play a significant role in cancer progression by changing cellular functions through the modulation of protein expressions. The potential of different miRNAs to alter the expression of the mammalian target of rapamycin (mTOR)/protein kinase B (PKB or AKT)/phosphatidylinositol‐3‐kinase (PI3K) signaling cascade, a key pathway in the progression of acute myeloid leukemia (AML), has been demonstrated across different types of cancers. Aims This study aims to explore the effects of miR‐100 and miR‐101 on the mTOR/AKT/PI3K signaling pathway in AML. Methods and Results Initially, we employed the TargetScan, miRDB, and miRanda databases to identify the target proteins of miR‐100 and miR‐101. Following a comprehensive analysis, we identified the mTOR/AKT/PI3K signaling pathway as a significant target for investigation in patients with AML. In this case–control study, the expression levels of miRNAs and genes were analyzed in 21 AML patients and 9 healthy controls using quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The results showed that miR‐100 was significantly upregulated, while miR‐101, mTOR, and PI3K were downregulated in AML patients. Correlation analysis revealed a negative relationship for miR‐100 and a positive one for miR‐101 with mTOR, but no significant correlation with AKT1 and PI3K genes. Conclusion These findings suggest that both miR‐100 and miR‐101 act as tumor suppressors via the mTOR/AKT/PI3K signaling pathway, highlighting their potential as therapeutic targets in AML.
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spelling doaj-art-505f1aba7ab24423a36da4e071e4ebdf2025-08-26T06:00:41ZengWileyCancer Reports2573-83482025-08-0188n/an/a10.1002/cnr2.70264Targeting the mTOR Signaling Pathway Through miR‐100 and miR‐101 in De Novo Acute Myeloid Leukemia: Implications for Therapeutic InterventionMaryam Kargar0Mehdi Allahbakhshian Farsani1Javad Garavand2Mahnaz Gorji3Mohammad Rafiee4Seyed Sobhan Bahreiny5Mohammad Hossein Mohammadi6Department of Laboratory Hematology and Blood Bank, School of Allied Medical Science Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Laboratory Hematology and Blood Bank, School of Allied Medical Science Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Laboratory Sciences, School of Allied Medical Sciences Ahvaz Jundishapur University of Medical Sciences Ahvaz IranDepartment of Laboratory Hematology and Blood Bank, School of Allied Medical Science Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Medical Laboratory Sciences, School of Para Medicine Hamadan University of Medical Sciences Hamadan IranMedical Basic Sciences Research Institute, Physiology Research Center, Department of Physiology, School of Medicine Ahvaz Jundishapur University of Medical Sciences Ahvaz IranHSCT Research Center, Laboratory Hematology and Blood Banking Department, School of Allied Medical Sciences Shahid Beheshti University of Medical Sciences Tehran IranABSTRACT Background Microribonucleic acid (MicroRNAs/miRNAs) play a significant role in cancer progression by changing cellular functions through the modulation of protein expressions. The potential of different miRNAs to alter the expression of the mammalian target of rapamycin (mTOR)/protein kinase B (PKB or AKT)/phosphatidylinositol‐3‐kinase (PI3K) signaling cascade, a key pathway in the progression of acute myeloid leukemia (AML), has been demonstrated across different types of cancers. Aims This study aims to explore the effects of miR‐100 and miR‐101 on the mTOR/AKT/PI3K signaling pathway in AML. Methods and Results Initially, we employed the TargetScan, miRDB, and miRanda databases to identify the target proteins of miR‐100 and miR‐101. Following a comprehensive analysis, we identified the mTOR/AKT/PI3K signaling pathway as a significant target for investigation in patients with AML. In this case–control study, the expression levels of miRNAs and genes were analyzed in 21 AML patients and 9 healthy controls using quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The results showed that miR‐100 was significantly upregulated, while miR‐101, mTOR, and PI3K were downregulated in AML patients. Correlation analysis revealed a negative relationship for miR‐100 and a positive one for miR‐101 with mTOR, but no significant correlation with AKT1 and PI3K genes. Conclusion These findings suggest that both miR‐100 and miR‐101 act as tumor suppressors via the mTOR/AKT/PI3K signaling pathway, highlighting their potential as therapeutic targets in AML.https://doi.org/10.1002/cnr2.70264acute myeloid leukemiamicroRNA‐100microRNA‐101mTOR/AKT/PI3K pathway
spellingShingle Maryam Kargar
Mehdi Allahbakhshian Farsani
Javad Garavand
Mahnaz Gorji
Mohammad Rafiee
Seyed Sobhan Bahreiny
Mohammad Hossein Mohammadi
Targeting the mTOR Signaling Pathway Through miR‐100 and miR‐101 in De Novo Acute Myeloid Leukemia: Implications for Therapeutic Intervention
Cancer Reports
acute myeloid leukemia
microRNA‐100
microRNA‐101
mTOR/AKT/PI3K pathway
title Targeting the mTOR Signaling Pathway Through miR‐100 and miR‐101 in De Novo Acute Myeloid Leukemia: Implications for Therapeutic Intervention
title_full Targeting the mTOR Signaling Pathway Through miR‐100 and miR‐101 in De Novo Acute Myeloid Leukemia: Implications for Therapeutic Intervention
title_fullStr Targeting the mTOR Signaling Pathway Through miR‐100 and miR‐101 in De Novo Acute Myeloid Leukemia: Implications for Therapeutic Intervention
title_full_unstemmed Targeting the mTOR Signaling Pathway Through miR‐100 and miR‐101 in De Novo Acute Myeloid Leukemia: Implications for Therapeutic Intervention
title_short Targeting the mTOR Signaling Pathway Through miR‐100 and miR‐101 in De Novo Acute Myeloid Leukemia: Implications for Therapeutic Intervention
title_sort targeting the mtor signaling pathway through mir 100 and mir 101 in de novo acute myeloid leukemia implications for therapeutic intervention
topic acute myeloid leukemia
microRNA‐100
microRNA‐101
mTOR/AKT/PI3K pathway
url https://doi.org/10.1002/cnr2.70264
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