Background:
The Notch signaling pathway has a key role in angiogenesis and Delta-Like Ligand 4 (DLL4) is
one of the main ligands of Notch involved in cell proliferation in sprouting vessels.
Objective:
In this study, we aimed to evaluate the expression of DLL4 in primary breast tumors and to examine the effect
of melatonin on DLL4 expression in vitro.
Methods:
Eighty-five breast tumor and paired adjacent non-tumor tissue samples were collected. Apoptosis assay was
performed on breast cancer cells to evaluate melatonin effects. Western blot and quantitative RT-PCR were used to
measure DLL4 expression. Then, we investigated the effect of melatonin on the expression of DLL4 in four breast cancer
cell lines at RNA and protein levels. We also performed Probabilistic Neural Network analysis to study genes closely
associated with DLL4 expression.
Results:
Our results showed a significantly higher expression of DLL4 in tumor tissues as compared to non-tumor tissues
(P = 0.027). Melatonin treatment substantially attenuated DLL4 expression in BT474 and MCF-7 cells, but not in SK-BR3 and MDA-MB-231 cells. Also, melatonin induced apoptosis in all four cell lines. Network analysis revealed a set of 15
genes that had close association and interaction with DLL4. DLL4 was overexpressed in breast cancer tissues as
compared to the non-tumor tissues.
Conclusion:
It can be concluded that melatonin treatment attenuated DLL4 expression only in estrogen-responsive breast
cancer cells and is able to induce apoptosis in breast cancer cells.
Cancer cells reprogram their metabolisms to achieve high energetic requirements and produce precursors that facilitate uncontrolled cell proliferation. Metabolic reprograming involves not only the dysregulation in glucose-metabolizing regulatory enzymes, but also the enzymes engaging in the lipid and amino acid metabolisms. Nevertheless, the underlying regulatory mechanisms of reprograming are not fully understood. Non-coding RNAs (ncRNAs) as functional RNA molecules cannot translate into proteins, but they do play a regulatory role in gene expression. Moreover, ncRNAs have been demonstrated to be implicated in the metabolic modulations in breast cancer (BC) by regulating the metabolic-related enzymes. Here, we will focus on the regulatory involvement of ncRNAs (microRNA, circular RNA and long ncRNA) in BC metabolism, including glucose, lipid and glutamine metabolism. Investigation of this aspect may not only alter the approaches of BC diagnosis and prognosis, but may also open a new avenue in using ncRNA-based therapeutics for BC treatment by targeting different metabolic pathways.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.