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CLC number: R737.31

On-line Access: 2019-03-01

Received: 2018-03-29

Revision Accepted: 2018-12-11

Crosschecked: 2019-01-09

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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.3 P.219-237


MiR-1180 from bone marrow-derived mesenchymal stem cells induces glycolysis and chemoresistance in ovarian cancer cells by upregulating the Wnt signaling pathway

Author(s):  Zhuo-Wei Gu, Yi-Feng He, Wen-Jing Wang, Qi Tian, Wen Di

Affiliation(s):  Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; more

Corresponding email(s):   he_yifeng@hotmail.com, diwen163@163.com

Key Words:  Chemoresistant ovarian cancer, Mesenchymal stem cell, MiR-1180, Secreted frizzled-related protein 1 (SFRP1), Wnt, Glycolysis

Zhuo-Wei Gu, Yi-Feng He, Wen-Jing Wang, Qi Tian, Wen Di. MiR-1180 from bone marrow-derived mesenchymal stem cells induces glycolysis and chemoresistance in ovarian cancer cells by upregulating the Wnt signaling pathway[J]. Journal of Zhejiang University Science B, 2019, 20(3): 219-237.

@article{title="MiR-1180 from bone marrow-derived mesenchymal stem cells induces glycolysis and chemoresistance in ovarian cancer cells by upregulating the Wnt signaling pathway",
author="Zhuo-Wei Gu, Yi-Feng He, Wen-Jing Wang, Qi Tian, Wen Di",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T MiR-1180 from bone marrow-derived mesenchymal stem cells induces glycolysis and chemoresistance in ovarian cancer cells by upregulating the Wnt signaling pathway
%A Zhuo-Wei Gu
%A Yi-Feng He
%A Wen-Jing Wang
%A Qi Tian
%A Wen Di
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 3
%P 219-237
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1800190

T1 - MiR-1180 from bone marrow-derived mesenchymal stem cells induces glycolysis and chemoresistance in ovarian cancer cells by upregulating the Wnt signaling pathway
A1 - Zhuo-Wei Gu
A1 - Yi-Feng He
A1 - Wen-Jing Wang
A1 - Qi Tian
A1 - Wen Di
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 3
SP - 219
EP - 237
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1800190

Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in cancer development and progression. However, the mechanism by which they enhance the chemoresistance of ovarian cancer is unknown. Methods: Conditioned media of BM-MSCs (BM-MSC-CM) were analyzed using a technique based on microRNA arrays. The most highly expressed microRNAs were selected for testing their effects on glycolysis and chemoresistance in SKOV3 and COC1 ovarian cancer cells. The targeted gene and related signaling pathway were investigated using in silico analysis and in vitro cancer cell models. Kaplan-Merier survival analysis was performed on a population of 59 patients enrolled to analyze the clinical significance of microRNA findings in the prognosis of ovarian cancer. Results: miR-1180 was the most abundant microRNA detected in BM-MSC-CM, which simultaneously induces glycolysis and chemoresistance (against cisplatin) in ovarian cancer cells. The secreted frizzled-related protein 1 (SFRP1) gene was identified as a major target of miR-1180. The overexpression of miR-1180 led to the activation of wnt signaling and its downstream components, namely wnt5a, β-catenin, c-Myc, and CyclinD1, which are responsible for glycolysis-induced chemoresistance. The miR-1180 level was inversely correlated with SFRP1 mRNA expression in ovarian cancer tissue. The overexpressed miR-1180 was associated with a poor prognosis for the long-term (96-month) survival of ovarian cancer patients. Conclusions: BM-MSCs enhance the chemoresistance of ovarian cancer by releasing miR-1180. The released miR-1180 activates the wnt signaling pathway in cancer cells by targeting SFRP1. The enhanced wnt signaling upregulates the glycolytic level (i.e. Warburg effect), which reinforces the chemoresistance property of ovarian cancer cells.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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