Centrosome‑, mitotic spindle‑ and cytokinetic bridge‑specific compartmentalization of AGO2 protein in human liver cells undergoing mitosis: Non‑canonical, RNAi‑dependent, control of local homeostasis

Theotoki,Eleni I.; Kakoulidis,Panos; Nikolakopoulos,Konstantinos-Stylianos; Vlachou,Eleni N.; Tsitsilonis,Ourania E.; Voutsinas,Gerassimos E.; Anastasiadou,Ema; Stravopodis,Dimitrios J.

doi:10.3892/mmr.2025.13609

Centrosome‑, mitotic spindle‑ and cytokinetic bridge‑specific compartmentalization of AGO2 protein in human liver cells undergoing mitosis: Non‑canonical, RNAi‑dependent, control of local homeostasis

Authors:
- Eleni I. Theotoki
- Panos Kakoulidis
- Konstantinos-Stylianos Nikolakopoulos
- Eleni N. Vlachou
- Ourania E. Tsitsilonis
- Gerassimos E. Voutsinas
- Ema Anastasiadou
- Dimitrios J. Stravopodis
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Affiliations: Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, Athens 15701, Greece, Department of Cancer Genetics, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece, Section of Animal and Human Physiology, Department of Biology, School of Science, National and Kapodistrian University of Athens, Athens 15701, Greece, Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research ‘Demokritos’, Athens 15310, Greece
Published online on: July 7, 2025 https://doi.org/10.3892/mmr.2025.13609
Article Number: 244
Copyright: © Theotoki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Argonaute RNA‑induced silencing complex catalytic component 2 (AGO2) is an evolutionary conserved protein involved in microRNA‑dependent gene expression regulation via the RNA interference (RNAi) mechanism. Nevertheless, AGO2 may also be involved in other key processes, such as histone modification, DNA methylation and alternative splicing. Its role in the proper development of organisms is key and no homologue is able to compensate for its loss. Therefore, using advanced immunofluorescence, transient transfection and molecular bioinformatics, the present study aimed to investigate novel, non‑canonical, RNAi‑dependent functions of AGO2 protein in mRNA/protein local homeostasis. The data revealed microtubule network‑dependent, localization of AGO2 in both centrosome and mitotic spindle assemblies during cell division and in the cytokinetic bridge formed during the last stage of mitosis (cytokinesis). Detection of AGO2 protein in these mitosis‑specific compartments, regardless of the presence of malignant phenotypes or multiple centrosomes/mitotic spindles in liver cells, indicates the cardinal role of AGO2 in centrosome biosynthesis, mitotic spindle formation and function, potentially controlling locality‑dependent homeostasis, in a novel non‑canonical, RNAi‑dependent manner. This novel AGO2/centrosome/mitotic spindle/cytokinetic bridge pathway may serve as a versatile molecular ‘toolbox’ for targeted therapy of human malignancy, including liver cancer.

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