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Interplay of miR-542, miR-126, miR-143 and miR-26b with PI3K-Akt is a Diagnostic Signal and Putative Regulatory Target in HPV-Positive Cervical Cancer

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Human papillomavirus accounts for 99.7% of all cervical cancer cases worldwide. The viral oncoproteins alter normal cell signaling and gene expression, resulting in loss of cell cycle control and cancer development. Also, microRNAs (miRNAs) have been reported to play a critical role in cervical carcinogenesis. Especially these are not only appropriate targets for therapeutic intervention in cervical cancer but also early diagnostic signals. The given study tries to improve the sparse knowledge on miRNAs and their role in this physiological context. Deregulated miRNAs were identified by analyzing the raw data of the well-founded GSE20592 dataset including 16 tumor/normal pairs of human cervical tissue samples. The dataset was quantified by a conservative strategy based on HTSeq and Salmon, followed by target prediction via TargetScan and miRDB. The comprehensive pathway analysis of all factors was performed using DAVID. The theoretical results were subject of a stringent experimental validation in a well-characterized clinical cohort of 30 tumor/normal pairs of cervical samples. The top 31 miRNAs and their 140 primary target genes were closely intertwined with the PI3K-Akt signaling pathway. MiR-21-3p and miR-1-3p showed a prominent regulatory role while miR-542, miR-126, miR-143, and miR-26b are directly targeting both PI3K and AKT. This study provides insights into the regulation of PI3K-Akt signaling as an important inducer of cervical cancer and identified miR-542, miR-126, miR-143, and miR-26b as promising inhibitors of the PI3K-Akt action.

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The data that support the findings of this study are available within the paper and Online Resource 1 or on request from the authors.


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The authors wish to thank all patients who participated in this study.


This study was supported by faculty research grants of the Alzahra University.

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Authors and Affiliations



Akram Rahimi-Moghaddam: Performed the bioinformatics analyses and experiments and wrote the manuscript. Nassim Ghorbanmehr: Supervised and designed the study, wrote the manuscript, and performed data analysis. Sedigheh Gharbi and Eberhard Korsching: Data analysis and review of the manuscript. Fatemeh Nili: Sample preparation and manuscript review. All the authors have read and approved the final manuscript.

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Correspondence to Nassim Ghorbanmehr.

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The authors declare no financial or non-financial interests that might influence the results and/or discussion reported in this paper.

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All experiments involving human samples were reviewed and approved by the Ethics Committee of Alzahra University (IR.ALZAHRA.REC.1400.058).

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Informed consent was obtained from all patients prior to the use of the samples for scientific research.

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Rahimi-Moghaddam, A., Ghorbanmehr, N., Gharbi, S. et al. Interplay of miR-542, miR-126, miR-143 and miR-26b with PI3K-Akt is a Diagnostic Signal and Putative Regulatory Target in HPV-Positive Cervical Cancer. Biochem Genet (2024).

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