Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis
Abstract Background Recent studies have reported the involvement of microRNA-29 (miR-29) family members in human cancers through their ability to regulate cellular functions. The present study investigated biological function of miR-29b in colorectal cancer (CRC). Methods CRC tissues and adjacent no...
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doaj-1057666319b14eab9101286aa381aebf2021-01-10T12:31:14ZengBMCCancer Cell International1475-28672021-01-0121111910.1186/s12935-020-01700-2Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axisYin Leng0Zhixian Chen1Hui Ding2Xiaoxu Zhao3Li Qin4Yunlong Pan5Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan UniversityDepartment of Oncology, Fuda Cancer Hospital, Jinan UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan UniversityMedical Department, The First Affiliated Hospital of Jinan UniversityDepartment of Histology and Embryology, Medical School of Jinan UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan UniversityAbstract Background Recent studies have reported the involvement of microRNA-29 (miR-29) family members in human cancers through their ability to regulate cellular functions. The present study investigated biological function of miR-29b in colorectal cancer (CRC). Methods CRC tissues and adjacent normal tissues were collected and the expression of ETV4 and miR-29b in the tissues were identified. The relationship between ETV4 and miR-29b or ETV4 expression and the EGFR promoter was identified using dual-luciferase reporter gene and CHIP assays. The proliferation, invasion, migration, and apoptosis of CRC HCT116 cells were assayed using MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. Also, expression of epithelial-mesenchymal transition (EMT) markers, angiogenic factors, and vasculogenic mimicry formation were evaluated using RT-qPCR and Western blot. Results ETV4 was upregulated, while miR-29b expression was decreased in CRC tissues. ETV4 was identified as a target gene of miR-29b, which in turn inactivated the ERK signaling pathway by targeting ETV4 and inhibiting EGFR transcription. Transfection with miR-29b mimic, siRNA-ETV4, or ERK signaling pathway inhibitor U0126 increased expression of E-cadherin and TSP-1, and CRC cell apoptosis, yet reduced expression of ERK1/2, MMP-2, MMP-9, Vimentin, and VEGF, as well as inhibiting EMT, angiogenesis, and CRC cell migration and invasion. The EMT, angiogenesis and cancer progression induced by miR-29b inhibitor were reversed by siRNA-mediated ETV4 silencing. Conclusions miR-29b suppresses angiogenesis and EMT in CRC via the ETV4/ERK/EGFR axis.https://doi.org/10.1186/s12935-020-01700-2Colorectal cancerMicroRNA-29bETV4ERK signaling pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yin Leng Zhixian Chen Hui Ding Xiaoxu Zhao Li Qin Yunlong Pan |
spellingShingle |
Yin Leng Zhixian Chen Hui Ding Xiaoxu Zhao Li Qin Yunlong Pan Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis Cancer Cell International Colorectal cancer MicroRNA-29b ETV4 ERK signaling pathway |
author_facet |
Yin Leng Zhixian Chen Hui Ding Xiaoxu Zhao Li Qin Yunlong Pan |
author_sort |
Yin Leng |
title |
Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis |
title_short |
Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis |
title_full |
Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis |
title_fullStr |
Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis |
title_full_unstemmed |
Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis |
title_sort |
overexpression of microrna-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the etv4/erk/egfr axis |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2021-01-01 |
description |
Abstract Background Recent studies have reported the involvement of microRNA-29 (miR-29) family members in human cancers through their ability to regulate cellular functions. The present study investigated biological function of miR-29b in colorectal cancer (CRC). Methods CRC tissues and adjacent normal tissues were collected and the expression of ETV4 and miR-29b in the tissues were identified. The relationship between ETV4 and miR-29b or ETV4 expression and the EGFR promoter was identified using dual-luciferase reporter gene and CHIP assays. The proliferation, invasion, migration, and apoptosis of CRC HCT116 cells were assayed using MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. Also, expression of epithelial-mesenchymal transition (EMT) markers, angiogenic factors, and vasculogenic mimicry formation were evaluated using RT-qPCR and Western blot. Results ETV4 was upregulated, while miR-29b expression was decreased in CRC tissues. ETV4 was identified as a target gene of miR-29b, which in turn inactivated the ERK signaling pathway by targeting ETV4 and inhibiting EGFR transcription. Transfection with miR-29b mimic, siRNA-ETV4, or ERK signaling pathway inhibitor U0126 increased expression of E-cadherin and TSP-1, and CRC cell apoptosis, yet reduced expression of ERK1/2, MMP-2, MMP-9, Vimentin, and VEGF, as well as inhibiting EMT, angiogenesis, and CRC cell migration and invasion. The EMT, angiogenesis and cancer progression induced by miR-29b inhibitor were reversed by siRNA-mediated ETV4 silencing. Conclusions miR-29b suppresses angiogenesis and EMT in CRC via the ETV4/ERK/EGFR axis. |
topic |
Colorectal cancer MicroRNA-29b ETV4 ERK signaling pathway |
url |
https://doi.org/10.1186/s12935-020-01700-2 |
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