miR‐130a‐3p regulated TGF‐β1‐induced epithelial‐mesenchymal transition depends on SMAD4 in EC‐1 cells

Abstract Metastasis and invasion are the primary causes of malignant progression in esophageal squamous cell carcinoma (ESCC). Epithelial‐mesenchymal transition (EMT) is crucial step of acquisition of "stemness" properties in tumor cells. However, the mechanism of esophageal cancer metasta...

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Main Authors: Xiaokang Tian, Qian Fei, Mingyu Du, Hongming Zhu, Jinjun Ye, Luxi Qian, Zhiwei Lu, Wenjun Zhang, Yan Wang, Fanyu Peng, Jie Chen, Baoling Liu, Qian Li, Xia He, Li Yin
Format: Article
Language:English
Published: Wiley 2019-03-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.1981
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author Xiaokang Tian
Qian Fei
Mingyu Du
Hongming Zhu
Jinjun Ye
Luxi Qian
Zhiwei Lu
Wenjun Zhang
Yan Wang
Fanyu Peng
Jie Chen
Baoling Liu
Qian Li
Xia He
Li Yin
author_facet Xiaokang Tian
Qian Fei
Mingyu Du
Hongming Zhu
Jinjun Ye
Luxi Qian
Zhiwei Lu
Wenjun Zhang
Yan Wang
Fanyu Peng
Jie Chen
Baoling Liu
Qian Li
Xia He
Li Yin
author_sort Xiaokang Tian
collection DOAJ
description Abstract Metastasis and invasion are the primary causes of malignant progression in esophageal squamous cell carcinoma (ESCC). Epithelial‐mesenchymal transition (EMT) is crucial step of acquisition of "stemness" properties in tumor cells. However, the mechanism of esophageal cancer metastasis remains unclear. This research was designed to explore the role and mechanism of SMAD4 and miR‐130a‐3p in the progression of transforming growth factor‐β (TGF‐β)‐induced EMT in vivo and in vitro. The expression of miR‐130a‐3p in ESCC cell line and normal esophageal epithelial cell was determined by RT‐qPCR. The protein expression levels of TGF‐β‐induced changes in EMT were analyzed by western blotting and immunofluorescence. Dual‐luciferase report assays were used to validate the regulation of miR‐130a‐3p‐SMAD4 axis. The effect of miR‐130a‐3p and SMAD4 in TGF‐β‐induced migration, invasion in the ESCC cell line EC‐1 was investigated by wound healing assays and Transwell assays. Here we found that knocked down SMAD4 could partially reverse TGF‐β‐induced migration, invasion, and EMT progression in the ESCC cell line EC‐1. miR‐130a‐3p, which directly targets SMAD4, is down‐regulated in ESCC. miR‐130a‐3p inhibits the migration and invasion of EC‐1 cells both in vitro and in vivo. Finally, miR‐130a‐3p inhibits TGF‐β‐induced EC‐1 cell migration, invasion, and EMT progression in a SMAD4‐dependent way. In conclusion, this study provides new insights into the mechanism underlying ESCC metastasis. The TGF‐β/miR‐130a‐3p/SMAD4 pathway could be potential targets for clinical treatment of ESCC.
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spelling doaj-art-7ff0d253a727425fb107dbe00bbcd9b22025-01-31T08:47:43ZengWileyCancer Medicine2045-76342019-03-01831197120810.1002/cam4.1981miR‐130a‐3p regulated TGF‐β1‐induced epithelial‐mesenchymal transition depends on SMAD4 in EC‐1 cellsXiaokang Tian0Qian Fei1Mingyu Du2Hongming Zhu3Jinjun Ye4Luxi Qian5Zhiwei Lu6Wenjun Zhang7Yan Wang8Fanyu Peng9Jie Chen10Baoling Liu11Qian Li12Xia He13Li Yin14Xuzhou Medical University Xuzhou Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaXuzhou Medical University Xuzhou Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaXuzhou Medical University Xuzhou Jiangsu ChinaJiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu ChinaAbstract Metastasis and invasion are the primary causes of malignant progression in esophageal squamous cell carcinoma (ESCC). Epithelial‐mesenchymal transition (EMT) is crucial step of acquisition of "stemness" properties in tumor cells. However, the mechanism of esophageal cancer metastasis remains unclear. This research was designed to explore the role and mechanism of SMAD4 and miR‐130a‐3p in the progression of transforming growth factor‐β (TGF‐β)‐induced EMT in vivo and in vitro. The expression of miR‐130a‐3p in ESCC cell line and normal esophageal epithelial cell was determined by RT‐qPCR. The protein expression levels of TGF‐β‐induced changes in EMT were analyzed by western blotting and immunofluorescence. Dual‐luciferase report assays were used to validate the regulation of miR‐130a‐3p‐SMAD4 axis. The effect of miR‐130a‐3p and SMAD4 in TGF‐β‐induced migration, invasion in the ESCC cell line EC‐1 was investigated by wound healing assays and Transwell assays. Here we found that knocked down SMAD4 could partially reverse TGF‐β‐induced migration, invasion, and EMT progression in the ESCC cell line EC‐1. miR‐130a‐3p, which directly targets SMAD4, is down‐regulated in ESCC. miR‐130a‐3p inhibits the migration and invasion of EC‐1 cells both in vitro and in vivo. Finally, miR‐130a‐3p inhibits TGF‐β‐induced EC‐1 cell migration, invasion, and EMT progression in a SMAD4‐dependent way. In conclusion, this study provides new insights into the mechanism underlying ESCC metastasis. The TGF‐β/miR‐130a‐3p/SMAD4 pathway could be potential targets for clinical treatment of ESCC.https://doi.org/10.1002/cam4.1981Epithelial‐mesenchymal transition (EMT)Esophageal squamous cell carcinoma (ESCC)SMAD4transforming growth factor‐β (TGF‐β)
spellingShingle Xiaokang Tian
Qian Fei
Mingyu Du
Hongming Zhu
Jinjun Ye
Luxi Qian
Zhiwei Lu
Wenjun Zhang
Yan Wang
Fanyu Peng
Jie Chen
Baoling Liu
Qian Li
Xia He
Li Yin
miR‐130a‐3p regulated TGF‐β1‐induced epithelial‐mesenchymal transition depends on SMAD4 in EC‐1 cells
Cancer Medicine
Epithelial‐mesenchymal transition (EMT)
Esophageal squamous cell carcinoma (ESCC)
SMAD4
transforming growth factor‐β (TGF‐β)
title miR‐130a‐3p regulated TGF‐β1‐induced epithelial‐mesenchymal transition depends on SMAD4 in EC‐1 cells
title_full miR‐130a‐3p regulated TGF‐β1‐induced epithelial‐mesenchymal transition depends on SMAD4 in EC‐1 cells
title_fullStr miR‐130a‐3p regulated TGF‐β1‐induced epithelial‐mesenchymal transition depends on SMAD4 in EC‐1 cells
title_full_unstemmed miR‐130a‐3p regulated TGF‐β1‐induced epithelial‐mesenchymal transition depends on SMAD4 in EC‐1 cells
title_short miR‐130a‐3p regulated TGF‐β1‐induced epithelial‐mesenchymal transition depends on SMAD4 in EC‐1 cells
title_sort mir 130a 3p regulated tgf β1 induced epithelial mesenchymal transition depends on smad4 in ec 1 cells
topic Epithelial‐mesenchymal transition (EMT)
Esophageal squamous cell carcinoma (ESCC)
SMAD4
transforming growth factor‐β (TGF‐β)
url https://doi.org/10.1002/cam4.1981
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