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

# metadata.dc.description.abstract[].value
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.

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Cell Death and Disease, 2025, vol. 16, num.1

# metadata.dc.rights[].value
cc-by (c)  Vidal-Sabanés, M. et al., 2025

# metadata.dc.source[].value
Articles publicats en revistes (Patologia i Terapèutica Experimental)

# metadata.dc.title[].value
Endometrial cancer progression driven by PTEN-deficiency requires miR-424(322)~503