**8.6 Role of micro-RNAs**

A newly opened window in cancer studies is the discovery of microRNAs (mi RNAs). It has been noticed that alteration of non-coding genes, including miRNAs is related to cancer pathogenesis. Mi RNAs modulate the expression of many genes through cleaving mRNA molecules or inhibiting their translation. As a result, they are involved in a variety of physiological and pathological processes, including development, differentiation, cellular proliferation, programmed cell death, cancer initiation and metastasis. It is important to note that a single miRNA can influence the expression of hundreds of proteins. Early studies showed that compared to normal breast human tissues, miRNAs are extensively deregulated in breast tumors. MiRNAs exert their influences at several steps of tumor development and metastasis. Cancer cell adherence, migration, invasion, motility, and angiogenesis are all affected by these modulators. "Metastamir" is the name which has been applied for the class of miRNAs which are involved in metastasis associated processes. Profiling of metastamirs in human breast cancer has been resulted in to find the new molecular mechanisms in metastatic process. Significant increase in expression of some of miRNAs has been identified in breast tumors and some others have shown some correlation with biopathological features such as Her2, ER and PR status, tumor stage, and response to treatments. The most important miRNAs involved in different steps of developing breast tumor are miR-335, miR-17/20, and miR-146 (involved inmicroenvironment modification), let-7, miR-200 and miR-30 (BCSC phenotype formation); miR-21,miR- 12 6, miR-373, and miR-520 (local invasion), miR-7, miR-661 and miR-17/20 (survival in vasculature ) and miR-200 and let-7 (proliferation at distant sites).

Chemoresistance is also affected by miRNAs. Some miRNAs which play some roles in this step are miR-125b, miR-21, and miR -128. The mechanisms underlying miRNAs dysregulation in breast cancer development, whether dysregulated miRNA is a cause or consequence of pathological and many other questions remain to be explored (55). Some of the most important miRNAs have been mentioned in table 1.


Table 1. miRNAs and their function in cancer
