Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling
Epithelial-to-mesenchymal transition (EMT) is a key process that occurs during tumor metastasis, affecting a variety of malignancies including colorectal cancer (CRC). Exosomes mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including microRNAs (miRNAs). Exos...
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Frontiers Media S.A.
2021-02-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.568738/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jian Bai Jian Bai Jian Bai Jian Bai Xue Zhang Xue Zhang Xue Zhang Xue Zhang Dongdong Shi Dongdong Shi Dongdong Shi Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Shuyi Wang Shuyi Wang Shuyi Wang Chaogang Yang Chaogang Yang Chaogang Yang Qing Liu Qing Liu Qing Liu Sihao Huang Sihao Huang Sihao Huang Yan Fang Yan Fang Yan Fang Weisong Zhang Weisong Zhang Weisong Zhang Jialin Song Jialin Song Jialin Song Bin Xiong Bin Xiong Bin Xiong |
spellingShingle |
Jian Bai Jian Bai Jian Bai Jian Bai Xue Zhang Xue Zhang Xue Zhang Xue Zhang Dongdong Shi Dongdong Shi Dongdong Shi Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Shuyi Wang Shuyi Wang Shuyi Wang Chaogang Yang Chaogang Yang Chaogang Yang Qing Liu Qing Liu Qing Liu Sihao Huang Sihao Huang Sihao Huang Yan Fang Yan Fang Yan Fang Weisong Zhang Weisong Zhang Weisong Zhang Jialin Song Jialin Song Jialin Song Bin Xiong Bin Xiong Bin Xiong Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling Frontiers in Cell and Developmental Biology microRNA EMT extracellular vesicle molecular signaling gastrointestinal |
author_facet |
Jian Bai Jian Bai Jian Bai Jian Bai Xue Zhang Xue Zhang Xue Zhang Xue Zhang Dongdong Shi Dongdong Shi Dongdong Shi Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Shuyi Wang Shuyi Wang Shuyi Wang Chaogang Yang Chaogang Yang Chaogang Yang Qing Liu Qing Liu Qing Liu Sihao Huang Sihao Huang Sihao Huang Yan Fang Yan Fang Yan Fang Weisong Zhang Weisong Zhang Weisong Zhang Jialin Song Jialin Song Jialin Song Bin Xiong Bin Xiong Bin Xiong |
author_sort |
Jian Bai |
title |
Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling |
title_short |
Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling |
title_full |
Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling |
title_fullStr |
Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling |
title_full_unstemmed |
Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling |
title_sort |
exosomal mir-128-3p promotes epithelial-to-mesenchymal transition in colorectal cancer cells by targeting foxo4 via tgf-β/smad and jak/stat3 signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-02-01 |
description |
Epithelial-to-mesenchymal transition (EMT) is a key process that occurs during tumor metastasis, affecting a variety of malignancies including colorectal cancer (CRC). Exosomes mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including microRNAs (miRNAs). Exosomal delivery of miRNAs plays an important role in tumor initiation, development, and progression. In this study, we investigated the effect of exosomal transfer between CRC cells and aimed to identify specific miRNAs and downstream targets involved in EMT and metastasis in CRC cells. High expression of miR-128-3p was identified in exosomes derived from EMT-induced HCT-116 cells. Altered miR-128-3p expression in CRC cells led to distinct changes in proliferation, migration, invasion, and EMT. Mechanistically, miR-128-3p overexpression downregulated the expression of FOXO4 and induced the activation of TGF-β/SMAD and JAK/STAT3 signaling in CRC cells and xenografted tumors, which led to EMT. Clinically, high expression of miR-128-3p was significantly associated with perineural invasion, lymphovascular invasion, tumor stage, and CA 19-9 content in CRC patients. We revealed that exosomal miR-128-3p regulates EMT by directly suppressing its downstream target gene FOXO4 to activate TGF-β/SMAD and JAK/STAT3 signaling, and the properties of the miR-128-3p/FOXO4 axis were horizontally transferred via exosomal delivery. In turn, exosomal miR-128-3p could be considered as a new therapeutic vehicle for CRC. |
topic |
microRNA EMT extracellular vesicle molecular signaling gastrointestinal |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.568738/full |
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doaj-f12dc5247d564b7e8e2f4739a4a9c4d02021-02-09T06:17:36ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.568738568738Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 SignalingJian Bai0Jian Bai1Jian Bai2Jian Bai3Xue Zhang4Xue Zhang5Xue Zhang6Xue Zhang7Dongdong Shi8Dongdong Shi9Dongdong Shi10Zhenxian Xiang11Zhenxian Xiang12Zhenxian Xiang13Shuyi Wang14Shuyi Wang15Shuyi Wang16Chaogang Yang17Chaogang Yang18Chaogang Yang19Qing Liu20Qing Liu21Qing Liu22Sihao Huang23Sihao Huang24Sihao Huang25Yan Fang26Yan Fang27Yan Fang28Weisong Zhang29Weisong Zhang30Weisong Zhang31Jialin Song32Jialin Song33Jialin Song34Bin Xiong35Bin Xiong36Bin Xiong37Department of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Anesthesiology, Peking University Third Hospital, Beijing, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of General Practice, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Radiation Oncology and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaEpithelial-to-mesenchymal transition (EMT) is a key process that occurs during tumor metastasis, affecting a variety of malignancies including colorectal cancer (CRC). Exosomes mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including microRNAs (miRNAs). Exosomal delivery of miRNAs plays an important role in tumor initiation, development, and progression. In this study, we investigated the effect of exosomal transfer between CRC cells and aimed to identify specific miRNAs and downstream targets involved in EMT and metastasis in CRC cells. High expression of miR-128-3p was identified in exosomes derived from EMT-induced HCT-116 cells. Altered miR-128-3p expression in CRC cells led to distinct changes in proliferation, migration, invasion, and EMT. Mechanistically, miR-128-3p overexpression downregulated the expression of FOXO4 and induced the activation of TGF-β/SMAD and JAK/STAT3 signaling in CRC cells and xenografted tumors, which led to EMT. Clinically, high expression of miR-128-3p was significantly associated with perineural invasion, lymphovascular invasion, tumor stage, and CA 19-9 content in CRC patients. We revealed that exosomal miR-128-3p regulates EMT by directly suppressing its downstream target gene FOXO4 to activate TGF-β/SMAD and JAK/STAT3 signaling, and the properties of the miR-128-3p/FOXO4 axis were horizontally transferred via exosomal delivery. In turn, exosomal miR-128-3p could be considered as a new therapeutic vehicle for CRC.https://www.frontiersin.org/articles/10.3389/fcell.2021.568738/fullmicroRNAEMTextracellular vesiclemolecular signalinggastrointestinal |