MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1

Wnt/β-catenin signaling pathway influences embryonic development, cell polarity and adhesion, apoptosis and tumorigenesis. MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (mi...

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Veröffentlicht in:Oncology reports 2016-03, Vol.35 (3), p.1425-1432
Hauptverfasser: JIANG, QIAN, HE, MIAO, MA, MENG-TAO, WU, HUI-ZHE, YU, ZHAO-JIN, GUAN, SHU, JIANG, LONG-YANG, WANG, YAN, ZHENG, DA-DI, JIN, FENG, WEI, MIN-JIE
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container_end_page 1432
container_issue 3
container_start_page 1425
container_title Oncology reports
container_volume 35
creator JIANG, QIAN
HE, MIAO
MA, MENG-TAO
WU, HUI-ZHE
YU, ZHAO-JIN
GUAN, SHU
JIANG, LONG-YANG
WANG, YAN
ZHENG, DA-DI
JIN, FENG
WEI, MIN-JIE
description Wnt/β-catenin signaling pathway influences embryonic development, cell polarity and adhesion, apoptosis and tumorigenesis. MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. Taken together, our results suggest that miR-148a can suppress the migration and invasion of breast cancer cells by targeting WNT-1 and inhibiting Wnt/β-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis.
doi_str_mv 10.3892/or.2015.4502
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MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. 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MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. 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In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. Taken together, our results suggest that miR-148a can suppress the migration and invasion of breast cancer cells by targeting WNT-1 and inhibiting Wnt/β-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>26707142</pmid><doi>10.3892/or.2015.4502</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Apoptosis
beta Catenin - genetics
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell growth
Cell migration
Cell Movement - genetics
Development and progression
Female
Gene expression
Gene Expression Regulation, Neoplastic
Genetic aspects
Genetic regulation
Health aspects
Humans
invasion
Kinases
MCF-7 Cells
Metastasis
MicroRNA
MicroRNAs
MicroRNAs - genetics
migration
miR-148a
Neoplasm Invasiveness - genetics
Proteins
RNA, Messenger - biosynthesis
Rodents
Studies
Tumorigenesis
Tumors
Wnt Signaling Pathway - genetics
WNT-1
Wnt/β-catenin signaling pathway
Wnt1 Protein - genetics
Wnt1 Protein - metabolism
title MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1
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