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.