microRNA-130a suppresses breast cancer cell migration and invasion by targeting FOSL1 and upregulating ZO-1

Xiaowei Chen, Min Zhao, Jin Huang, Yuhuang Li, Shunqing Wang, Christina (Chris) Harrington, Zheng (David) Qian, Xiao-Xin Sun, Mushui Dai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

FOSL1 is frequently overexpressed in multiple types of human cancers including invasive breast cancers and implicated in cancer invasion and metastasis. However, how FOSL1 is overexpressed in cancers remains to be elucidated. Several microRNAs (miRNAs) have been shown to target FOSL1 and are downregulated in human cancers. Here, we report that miR-130a is a novel FOSL1 targeting miRNA. Using gene expression microarray analysis, we found that FOSL1 is among the most up-regulated genes in cells transfected with miR-130a inhibitors. Transient transfection-immunoblot, RNA-immunoprecipitation, and luciferase reporter assays revealed that miR-130a directly targets FOSL1 mRNA at its 3'-UTR. Overexpression of miR-130a significantly reduced the levels of FOSL1 in invasive breast cancer MDA-MB-231 and Hs578T cell lines and suppresses their migration and invasion. This inhibition can be rescued by ectopic expression of miR-130a-resistant FOSL1. Interestingly, we show that overexpression of miR-130a increased the levels of tight-junction protein ZO-1 while inhibition of miR-130a reduced the levels of ZO-1. We further show that miR-130a expression is significantly reduced in cancer tissues from triple-negative breast cancer (TNBC) patients, correlating significantly with the upregulation of FOSL1 expression, compared to non-TNBC tissues. Together, our results reveal that miR-130a directly targets FOSL1 and suppresses the inhibition of ZO-1, thus inhibiting cancer cell migration and invasion, in TNBCs.

Original languageEnglish (US)
JournalJournal of Cellular Biochemistry
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

MicroRNAs
Cell Movement
Zonula Occludens-1 Protein
Cells
Tissue
Breast Neoplasms
3' Untranslated Regions
Microarrays
Luciferases
Gene expression
Assays
Neoplasms
Genes
RNA
Messenger RNA
Triple Negative Breast Neoplasms
Microarray Analysis
Immunoprecipitation
Transfection
Up-Regulation

Keywords

  • Breast cancer
  • FOSL1
  • MiR-130a
  • Tight junction
  • ZO-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{eda4f61111c84115a7182f0a89261af3,
title = "microRNA-130a suppresses breast cancer cell migration and invasion by targeting FOSL1 and upregulating ZO-1",
abstract = "FOSL1 is frequently overexpressed in multiple types of human cancers including invasive breast cancers and implicated in cancer invasion and metastasis. However, how FOSL1 is overexpressed in cancers remains to be elucidated. Several microRNAs (miRNAs) have been shown to target FOSL1 and are downregulated in human cancers. Here, we report that miR-130a is a novel FOSL1 targeting miRNA. Using gene expression microarray analysis, we found that FOSL1 is among the most up-regulated genes in cells transfected with miR-130a inhibitors. Transient transfection-immunoblot, RNA-immunoprecipitation, and luciferase reporter assays revealed that miR-130a directly targets FOSL1 mRNA at its 3'-UTR. Overexpression of miR-130a significantly reduced the levels of FOSL1 in invasive breast cancer MDA-MB-231 and Hs578T cell lines and suppresses their migration and invasion. This inhibition can be rescued by ectopic expression of miR-130a-resistant FOSL1. Interestingly, we show that overexpression of miR-130a increased the levels of tight-junction protein ZO-1 while inhibition of miR-130a reduced the levels of ZO-1. We further show that miR-130a expression is significantly reduced in cancer tissues from triple-negative breast cancer (TNBC) patients, correlating significantly with the upregulation of FOSL1 expression, compared to non-TNBC tissues. Together, our results reveal that miR-130a directly targets FOSL1 and suppresses the inhibition of ZO-1, thus inhibiting cancer cell migration and invasion, in TNBCs.",
keywords = "Breast cancer, FOSL1, MiR-130a, Tight junction, ZO-1",
author = "Xiaowei Chen and Min Zhao and Jin Huang and Yuhuang Li and Shunqing Wang and Harrington, {Christina (Chris)} and Qian, {Zheng (David)} and Xiao-Xin Sun and Mushui Dai",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/jcb.26739",
language = "English (US)",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
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}

TY - JOUR

T1 - microRNA-130a suppresses breast cancer cell migration and invasion by targeting FOSL1 and upregulating ZO-1

AU - Chen, Xiaowei

AU - Zhao, Min

AU - Huang, Jin

AU - Li, Yuhuang

AU - Wang, Shunqing

AU - Harrington, Christina (Chris)

AU - Qian, Zheng (David)

AU - Sun, Xiao-Xin

AU - Dai, Mushui

PY - 2018/1/1

Y1 - 2018/1/1

N2 - FOSL1 is frequently overexpressed in multiple types of human cancers including invasive breast cancers and implicated in cancer invasion and metastasis. However, how FOSL1 is overexpressed in cancers remains to be elucidated. Several microRNAs (miRNAs) have been shown to target FOSL1 and are downregulated in human cancers. Here, we report that miR-130a is a novel FOSL1 targeting miRNA. Using gene expression microarray analysis, we found that FOSL1 is among the most up-regulated genes in cells transfected with miR-130a inhibitors. Transient transfection-immunoblot, RNA-immunoprecipitation, and luciferase reporter assays revealed that miR-130a directly targets FOSL1 mRNA at its 3'-UTR. Overexpression of miR-130a significantly reduced the levels of FOSL1 in invasive breast cancer MDA-MB-231 and Hs578T cell lines and suppresses their migration and invasion. This inhibition can be rescued by ectopic expression of miR-130a-resistant FOSL1. Interestingly, we show that overexpression of miR-130a increased the levels of tight-junction protein ZO-1 while inhibition of miR-130a reduced the levels of ZO-1. We further show that miR-130a expression is significantly reduced in cancer tissues from triple-negative breast cancer (TNBC) patients, correlating significantly with the upregulation of FOSL1 expression, compared to non-TNBC tissues. Together, our results reveal that miR-130a directly targets FOSL1 and suppresses the inhibition of ZO-1, thus inhibiting cancer cell migration and invasion, in TNBCs.

AB - FOSL1 is frequently overexpressed in multiple types of human cancers including invasive breast cancers and implicated in cancer invasion and metastasis. However, how FOSL1 is overexpressed in cancers remains to be elucidated. Several microRNAs (miRNAs) have been shown to target FOSL1 and are downregulated in human cancers. Here, we report that miR-130a is a novel FOSL1 targeting miRNA. Using gene expression microarray analysis, we found that FOSL1 is among the most up-regulated genes in cells transfected with miR-130a inhibitors. Transient transfection-immunoblot, RNA-immunoprecipitation, and luciferase reporter assays revealed that miR-130a directly targets FOSL1 mRNA at its 3'-UTR. Overexpression of miR-130a significantly reduced the levels of FOSL1 in invasive breast cancer MDA-MB-231 and Hs578T cell lines and suppresses their migration and invasion. This inhibition can be rescued by ectopic expression of miR-130a-resistant FOSL1. Interestingly, we show that overexpression of miR-130a increased the levels of tight-junction protein ZO-1 while inhibition of miR-130a reduced the levels of ZO-1. We further show that miR-130a expression is significantly reduced in cancer tissues from triple-negative breast cancer (TNBC) patients, correlating significantly with the upregulation of FOSL1 expression, compared to non-TNBC tissues. Together, our results reveal that miR-130a directly targets FOSL1 and suppresses the inhibition of ZO-1, thus inhibiting cancer cell migration and invasion, in TNBCs.

KW - Breast cancer

KW - FOSL1

KW - MiR-130a

KW - Tight junction

KW - ZO-1

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U2 - 10.1002/jcb.26739

DO - 10.1002/jcb.26739

M3 - Article

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

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