Extracellular vesicle‐encapsulated microRNA‐296‐3p from cancer‐associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways

Cancer‐associated fibroblasts (CAFs), as important components of the tumor microenvironment, can regulate intercellular communication and tumor development by secreting extracellular vesicles (EVs). However, the role of CAF‐derived EVs in ovarian cancer has not been fully elucidated. Here, using an...

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Bibliographic Details
Published in:Cancer science Vol. 115; no. 1; pp. 155 - 169
Main Authors: Sun, Luyao, Ke, Miaola, Yin, Mengyuan, Zeng, Ying, Ji, Yutong, Hu, Yiming, Fu, Songbin, Zhang, Chunyu
Format: Journal Article
Language:English
Published: England John Wiley & Sons, Inc 01.01.2024
John Wiley and Sons Inc
Subjects:
AKT protein
Angiogenesis
cancer progression
Cancer-Associated Fibroblasts
cancer‐associated fibroblast
Cell proliferation
Cell Proliferation - genetics
Cells
Chemoresistance
Chemotherapy
Communication
Drug resistance
extracellular vesicle
Extracellular vesicles
Extracellular Vesicles - genetics
Female
Fibroblasts
Gene amplification
Humans
Laboratory animals
Metastasis
MicroRNAs
MicroRNAs - genetics
miRNA
miR‐296‐3p
Original
Ovarian cancer
Ovarian Neoplasms - genetics
Phenotypes
Plasma
Proteins
Proto-Oncogene Proteins c-akt
PTEN Phosphohydrolase - genetics
PTEN protein
Sequence analysis
Stat3 protein
STAT3 Transcription Factor - genetics
Suppressor of Cytokine Signaling Proteins
Therapeutic targets
Transmission electron microscopy
Tumor cells
Tumor microenvironment
Tumor Microenvironment - genetics
Tumorigenesis
Womens health
cancer-associated fibroblast
cancer progression
miR-296-3p
ovarian cancer
extracellular vesicle
ISSN:1347-9032, 1349-7006, 1349-7006
Online Access:Get full text
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Summary:Cancer‐associated fibroblasts (CAFs), as important components of the tumor microenvironment, can regulate intercellular communication and tumor development by secreting extracellular vesicles (EVs). However, the role of CAF‐derived EVs in ovarian cancer has not been fully elucidated. Here, using an EV‐microRNA sequencing analysis, we reveal specific overexpression of microRNA (miR)‐296‐3p in activated CAF‐derived EVs, which can be transferred to tumor cells to regulate the malignant phenotypes of ovarian cancer cells. Moreover, overexpression of miR‐296‐3p significantly promotes the proliferation, migration, invasion, and drug resistance of ovarian cancer cells in vitro, as well as tumor growth in vivo, while its inhibition has the opposite effects. Further mechanistic studies reveal that miR‐296‐3p promotes ovarian cancer progression by directly targeting PTEN and SOCS6 and activating AKT and STAT3 signaling pathways. Importantly, increased expression of miR‐296‐3p encapsulated in plasma EVs is closely correlated with tumorigenesis and chemoresistance in patients with ovarian cancer. Our results highlight the cancer‐promoting role of CAF‐derived EVs carrying miR‐296‐3p in ovarian cancer progression for the first time, and suggest that miR‐296‐3p encapsulated in CAF‐derived EVs could be a diagnostic biomarker and therapeutic target for ovarian cancer.
Bibliography:Luyao Sun and Miaola Ke contributed equally to this work.
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ISSN:1347-9032
1349-7006
1349-7006
DOI:10.1111/cas.16014