4.2 Article

Nanog-mediated stem cell properties are critical for MBNL3-associated paclitaxel resistance of ovarian cancer

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JOURNAL OF BIOCHEMISTRY
卷 169, 期 6, 页码 747-756

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OXFORD UNIV PRESS
DOI: 10.1093/jb/mvab021

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MBNL3; Nanog; ovarian cancer; paclitaxel resistance; stem-like cells

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The study identified that high expression of MBNL3 in ovarian cancer patients is positively correlated with paclitaxel resistance and poor prognosis, as it increases cancer cell viability and decreases apoptosis in ovarian stem-like cells through upregulating Nanog gene expression, suggesting that the MBNL3-Nanog axis could be a potential therapeutic target for managing paclitaxel resistance in ovarian cancer.
Paclitaxel (PTX) is the standard first-line treatment of ovarian cancer, but its efficacy is limited by multidrug resistance. Therefore, it is crucial to identify effective drug targets to facilitate PTX sensitivity for ovarian cancer treatment. Seventy PTX-administrated ovarian cancer patients were recruited in this study for gene expression and survival rate analyses. Muscleblind-like-3 (MBNL3) gain-offunction and loss-of-function experiments were carried out in ovarian cancer cells (parental and PTXresistant) and xenograft model. Cancer cell viability, apoptosis, spheroids formation, Nanog gene silencing were examined and conducted to dissect the underlying mechanism of MBNL3-mediated PTX resistance. High expression of MBNL3 was positively correlated with PTX resistance and poor prognosis of ovarian cancer. MBNL3-increased cell viability and decreased apoptosis in ovarian stem-like cells, through upregulating Nanog. This study suggests the MBNL3-Nanog axis is a therapeutic target for the treatment of PTX resistance in ovarian cancer management.

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