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904828.pdf (17.49 MB)

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2025-10-06

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cc-by (c) Vidal-Sabanés, M. et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224357

Endometrial cancer progression driven by PTEN-deficiency requires miR-424(322)~503

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Recurs relacionat

https://doi.org/10.1038/s41419-025-08022-z

Resum

Endometrial cancer is the most frequent type of cancer in the female reproductive tract. Loss-of-function alterations in PTEN, leading to enhanced PI3K/AKT activation, are among the most frequent molecular alterations in endometrial cancer. Increased PI3K/AKT signaling resulting from PTEN loss promotes cellular proliferation and confers resistance to TGFβ-mediated apoptosis, a key regulator of endometrial homeostasis. In this study, we have analyzed the role of miRNAs in driving these altered cellular responses. A comprehensive transcriptomic analysis of miRNA expression revealed the upregulation of several miRNAs caused by PTEN deficiency and/or TGFβ stimulation. The miR-424(322)~503 cluster drew our attention due to its involvement in regulating apoptosis and proliferation. However, miR-424(322)~503 cluster has a paradoxical role in cancer, exhibiting either oncogenic and tumor suppressive functions depending on cell type or context. To ascertain the function of miR-424(322)~503 in endometrial carcinogenesis caused by PTEN deficiency, we generated a double Pten/miR-424(322)~503 knock-out mice. We demonstrate that loss of miR-424(322)~503 impairs proliferation of both wild type or Pten deficient endometrial organoids by interfering with growth factor and PI3K/AKT signaling. Furthermore, the absence of miR-424(322)~503 restores TGFβ-induced apoptosis, which is otherwise compromised by PTEN deficiency. In vivo, Pten/miR-424(322)~503 knock-out mice exhibit reduced endometrial cancer progression compared to Pten deficient mice through a cell-autonomous mechanism.

Matèries

Càncer d'endometri, Micro RNAs, Antioncogens

Matèries (anglès)

Endometrial cancer, MicroRNAs, Antioncogenes

Citació

Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

VIDAL SABANÉS, Maria, et al. Endometrial cancer progression driven by PTEN-deficiency requires miR-424(322)~503. Cell Death and Disease. 2025. Vol. 16, num. 1. ISSN 2041-4889. [consulted: 14 of August of 2026]. Available at: https://hdl.handle.net/2445/224357

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