Over the past couple of years research into miRNAs has become increasingly diversified and attracted a great number of research articles across genetics and medicine. This should hardly come as a surprise to any scientist in the field, especially since it has become clear that miRNAs, a recently discovered class of non-coding RNAS, are represented in nearly all cellular functions and molecular pathways. A growing list of reports demonstrates that microRNAs play a critical role in cancer initiation and progression, and that miRNA alterations are ubiquitous in human cancers. In fact, several studies have shown that miRNAs can act either as tumor suppressors or as oncogenes, and that measurement of miRNA expression in malignancies may have diagnostic implications or otherwise lead to novel treatments of breast cancer.
In the article "Mir-205 modulates acinar size and morphology of transformed breast epithelial cells" which will be released later this week in OncomiRs – an open access journal published by Versita, molecular biologists from CEA Saclay and Université Paris-Sud, led by Prof. Annick Harel-Bellan, studied the microRNAs expression potentially responsible for the abnormal acini formation of breast cancer cells. They observed that the overexpression of the miR-205 influences the morphology of acini, linking this miRNA to breast epithelial cell transformation.
A genome-wide microRNA expression screen comparing non-transformed and tumorigenic MCF10A cell lines identified miR-205 as a potential modifier of acinus size. Forced expression of miR-205 in non-transformed MCF10A cells increased the size of acini, whereas miR-205 antisense oligonucleotides restored a normal morphology. MiR-205 did not modify cell proliferation, but rather inhibited cell death by apoptosis. Moreover, miR-205 targets ZEB1, an inhibitor of E-cadherin. Downregulating E-cadherin restored normal acinar morphology in miR-205 expressing cells, consistent with E-cadherin being involved in the miR-205-dependent acini phenotype.
The researchers further examined critical cellular formation in breast cancer. It has been demonstrated that normal breast epithelial cells form highly organized multi-cellular structures - the breast lobules, terminating in acinar structures called alveoli, which can be mimicked in vitro in three-dimensional (3D) cultures. Moreover, breast epithelial cells self-organize to form "acini". The size and morphology of acini is highly dependent on the degree of cancerous transformation of breast epithelial cells. Transformed cell lines form larger acini than normal cells, and cancer cells do not form normal acini, but instead form much larger aggregates of cells with no well-defined lumen.
Commenting on the research results, Prof. Annick Harel-Bellan notes: ' miR-205 is definitely not a simple tumor-suppressor miRNA in breast as previously believed, but it can be overexpressed in transformed cells and can be responsible for the abnormally large morphology of acini.'
The research highlights the complexity of miR-205 function in breast epithelial cells: miR-205 can act not only as a tumor suppressor, as formerly proposed, but also as an oncogene that favors cell proliferation or represses cell death. "Consequently, the use of miR-205 as a curative miRNA in cancer, as previously suggested by others, should be approached with great caution" observes Harel-Bellan in her article. Without doubt, continuous efforts to identify and describe miRNAs will provide novel insights into breast cancer biology, and will eventually arrange for a new molecular target for alternative treatments.
Journal
OncomiRs