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From the journal: Metallomics. Why is it worth testing the ability of zinc to protect against ischaemia reperfusion injury for human application. This article is part of the themed collection: Recent Review Articles. You have access to this article. Please wait while we load your content Something went wrong.
Try again? Cited by. Back to tab navigation Download options Please wait Other examples are miR and miR, which act as negative regulators of metastasis and tumor invasion in lung and breast cancer[ , ]. Roles of microRNAs in cancer. An oncogenic miRNA, termed oncomiR, can repress the translation of a tumor suppressor gene, stimulating tumorigenesis and leading to tumor formation.
Conversely, a tumor suppressor miRNA is able to inhibit the expression of oncogenes, blocking the tumorigenesis process and consequently the development of cancer. This is not surprising considering that the same miRNA may regulate from ten to hundreds of genes involved in completely different cellular pathways.
If we consider miR, it works as an oncomiR in solid and hematological malignancies, such as lymphoma and breast cancer[ , ], but in melanoma, as well as in ovarian and gastric cancer, it shows a tumor suppressor role[ , ]. Another relevant example is represented by miR, which shows tumor suppressor properties in several cancers, like melanoma, osteosarcoma, ovarian and breast cancer, and tumor promoting functions in pancreatic and prostate cancers[ , ].
It is clear that the dual role of miRNAs could be due to the heterogeneity and variability of cancer, causing the same miRNA to carry out different effects in different tumors. In this context miRNAs expression can be used as a tool to predict tumorigenesis and overall survival, but also to classify malignant and non-malignant tissues. To date, the clinical importance of miRNAs has been demonstrated for several types of cancers and by using also biopsies or surgery specimens[ ].
To support this idea, to date, miRNA deregulation in serum of cancer patients has been described for several types of tumors such as leukemia, lymphoma, gastric, lung, ovarian, prostate, pancreatic and breast cancer[ ].
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Most miRNAs found outside of cells, particularly in body fluids, are stable, and this is quite surprising since most RNA molecules in the extracellular environment are subjected to ribonucleases. These observations suggest that secreted miRNAs could be protected by degradation possibly by being packed in particular extracellular vesicles[ ].
Among extracellular vesicles, exosomes turn out to be the most studied membrane bound vesicles released from cells into the extracellular space[ ]. Exosomes play an important role in exchanging information between cancer cells, and such cell-to-cell communication is essential for tumor survival and progression and for metastases formation.
Several studies identified exosomes as the key components of this process, and the idea that extracellular miRNA are among the mediators used by exosomes for this inter-cell communication makes this model even more attractive. In line with these data, several studies showed that exosomal miRNA expression is altered in cancer[ , ].
The function of exosomal miRNAs is poorly understood, but some reports showed that in this context they carry out their conventional role of negative regulators of gene expression. One example is miR which, once released from breast cancer cell lines, reduces ZO-1 gene expression and promotes metastases formation in the lung and brain[ ]. Recently, a novel and peculiar function of exosomal miR and miRa was demonstrated: Such miRNAs are capable to activate immune cells, by acting as toll-like receptors ligands[ ]. These observations and future progresses in the miRNA research field will be very helpful for the development of new therapeutical strategies to fight cancer.
Indeed, when a cancer is characterized by the overexpression of specific miRNAs, the use of anti-miRs as drugs could help restoring the non-pathological condition. On the contrary, the same results could be obtained by the use of miRNA mimics in cancers in which specific miRNAs are downregulated. A similar approach was described by Kota et al[ ]: The restoring of miRa in hepatocellular carcinoma is able to reduce cancer cell proliferation by triggering apoptosis.
These data widely show that miRNAs have a precious potential to act as therapeutical targets. In conclusions, the miRNA world is fascinating and mysterious. The number of miRNA genes that are being discovered is increasing and novel mechanisms of action might reveal possible new therapeutic strategies. The fact that miRNAs use non-canonical target sites to perform their function opens a puzzling scenario that could lead researchers to discover completely new miRNA functions and modes of action.
Although great strides have been made in the recent years, the comprehension of the global miRNome and the establishment of functional therapeutic strategies in miRNA cancer research are yet far from being achieved. The discovery and development of miRNA inhibitors or miRNA mimics as novel drugs will offer new hopes in the fight against cancer. Manuscript source: Invited manuscript. Specialty type: Biochemistry and molecular biology. Country of origin: Italy.
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First steps in qualitative data analysis: transcribing | Family Practice | Oxford Academic
Grade A Excellent : 0. Grade B Very good : B, B. Conflict-of-interest statement: Authors declare no conflict of interests for this article. Peer-review started: August 24, First decision: October 8, Article in press: January 18, National Center for Biotechnology Information , U.
World J Biol Chem. Published online Feb Author information Article notes Copyright and License information Disclaimer. Author contributions: Oliveto S collected the data and wrote the manuscript; Mancino M collected the data; Manfrini N and Biffo S critically revised the article. Published by Baishideng Publishing Group Inc.
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