Therapeutic Potential of Melatonin in the Regulation of MiR-148a-3p and Angiogenic Factors in Breast Cancer
Author:
Lacerda Jéssica Zani1, Ferreira Lívia Carvalho1, Lopes Beatriz Camargo1, Aristizábal-Pachón Andrés Felipe2, Bajgelman Marcio Chaim3, Borin Thaiz Ferraz4, de Campos Zuccari Debora Aparecida Pires1
Affiliation:
1. Laboratory of Molecular Research in Cancer (LIMC), Medical School of Sao Jose do Rio Preto (FAMERP), Sao Jose do Rio Preto (SP), Brazil 2. Laboratory of Molecular Genetics and Bioinformatics (LGMB), Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (FMRP/USP), Ribeirao Preto (SP), Brazil 3. Laboratory of Biosciences of the National Center of Research in Energy and Materials (LNBio/CNPEM), Campinas (SP), Brazil 4. Georgia Cancer Center, Augusta University, 1120 15th Street, Augusta, GA 30912, United States
Abstract
Background:
The high mortality rate of breast cancer is related to the occurrence of metastasis,
a process that is promoted by tumor angiogenesis. MicroRNAs are small molecules of noncoding
mRNA that play a key role in gene regulation and are directly involved in the progression and
angiogenesis of various tumor types, including breast cancer. Several miRNAs have been described
as promoters or suppressors angiogenesis and may be associated with tumor growth and metastasis.
Melatonin is an oncostatic agent with a capacity of modifying the expression of innumerable genes
and miRNAs related to cancer.
Objective:
The aim of this study was to evaluate the role of melatonin and the tumor suppressor miR-
148a-3p on angiogenesis of breast cancer.
Method:
MDA-MB-231 cells were treated with melatonin and modified with the overexpression of
miR-148a-3p. The relative quantification in real-time of miR-148a-3p, IGF-IR and VEGF was performed
by real-time PCR. The protein expression of these targets was performed by immunocytochemistry
and immunohistochemistry. Survival, migration and invasion rates of tumor cells were
evaluated. Finally, the xenograft model of breast cancer was performed to confirm the role of melatonin
in the tumor.
Results:
The melatonin was able to increase the gene level of miR-148a-3p and decreased the gene
and protein expression of IGF-1R and VEGF, both in vitro and in vivo. In addition, it also had an inhibitory
effect on the survival, migration and invasion of breast tumor cells.
Conclusion:
Our results confirm the role of melatonin in the regulation of miR-148a-3p and decrease
of angiogenic factors.
Funder
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
Publisher
Bentham Science Publishers Ltd.
Subject
Orthopedics and Sports Medicine,Emergency Medicine,General Medicine
Reference62 articles.
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