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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

10.1631/jzus.B1800190


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",
volume="20",
number="3",
pages="219-237",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1800190"
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%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

TY - JOUR
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


Abstract: 
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.

骨髓间充质干细胞释放miR-1180上调Wnt信号通路活性并促进卵巢癌细胞糖酵解和化疗耐药能力的研究

目的:已知骨髓间充质干细胞在癌症的发生发展中起有重要作用,本研究分析它们在增强卵巢癌化疗耐药能力中的具体作用.
创新点:发现骨髓间充质干细胞可以通过释放微小RNA(microRNA)影响卵巢癌化疗耐药能力,并确定了介导此作用的microRNA分子和相关作用机制.
方法:收集骨髓间充质干细胞条件培养基,以微阵列方法分析其中microRNA表达谱.针对所获高表达microRNA,分析它(们)对细胞内糖酵解及相关化疗耐药行为的影响.通过生物信息学方法查找所获microRNA的靶基因,分析信号作用机制.纳入59名卵巢癌患者,以Kaplan-Merier生存分析方法考察所获microRNA分子表达程度的临床预后意义.
结论:迁移至卵巢癌组织内的骨髓间充质干细胞可释放miR-1180分子.MiR-1180分子进入癌细胞后,识别并下调SFRP1蛋白(分泌型Wnt受体,起信号抑制作用),由此提高Wnt通路活性.活化后的Wnt信号通路可增强癌细胞内糖酵解水平(即Warburg效应),从而引起糖酵解依赖性化疗耐药行为.

关键词:卵巢癌化疗耐药;间充质干细胞;MiR-1180;SFRP1;Wnt;糖酵解

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

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