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Exosomal miR-122-3p represses the growth and metastasis of MCF-7/ADR cells by targeting GRK4-mediated activation of the Wnt/ß-catenin pathway.
Song, Binbin; Hou, Guoxin; Xu, Maoyi; Chen, Ming.
Affiliation
  • Song B; Department of Radiotherapy, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China.; Department of Medical Oncology, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang, China.
  • Hou G; Department of Medical Oncology, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang, China.
  • Xu M; Department of Medical Oncology, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang, China.
  • Chen M; Department of Radiotherapy, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China.. Electronic address: ab_wy2008@163.com.
Cell Signal ; 117: 111101, 2024 05.
Article de En | MEDLINE | ID: mdl-38365112
ABSTRACT
Breast cancer (BC) is a common cancer whose incidence continues to grow while its medical progress has stagnated. miRNAs are vital messengers that facilitate communications among different cancer cells. This study was to reveal the correlation of miR-122-3p expression with BC metastasis and Adriamycin (ADM) resistance and its mechanism of inhibiting BC metastasis. We found that expression of miR-122-3p is negatively correlated with BC metastasis and is lower in MCF-7/ADR cells. Overexpression of miR-122-3p in MCF-7/ADR cancer cells impairs their ability to migrate, invade, and stimulate blood vessel formation. Further research found that miR-122-3p directly binds to the 3' UTR of GRK4, reducing the phosphorylation of LRP6, which activates the Wnt/ß-catenin signaling pathway, facilitating BC development and metastasis. In addition, we observed that miR-122-3p is present in MCF-7  cells, and treatment of MCF-7/ADR cells with MCF-7-derived exosomes, but not with exosomes from miR-122-3p-deficient MCF-7 cells, has identical effects to miR-122-3p overexpression. Data from xenograft experiments further suggest that excess miR-122-3p and MCF-7-derived exosomes inhibit the growth and metastasis of MCF-7/ADR cancer cells in vivo. In conclusion our data reveal that exosomal miR-122-3p may negatively regulate BC growth and metastasis, potentially serving as a diagnostic and druggable target for BC treatment.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tumeurs du sein / MicroARN Limites: Female / Humans Langue: En Journal: Cell Signal Année: 2024 Type de document: Article Pays d'affiliation: Chine

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tumeurs du sein / MicroARN Limites: Female / Humans Langue: En Journal: Cell Signal Année: 2024 Type de document: Article Pays d'affiliation: Chine