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MicroRNAs (miRNAs) are endogenous, small non-coding RNA molecules that play important regulatory roles in numerous biological processes, cellular pathways and networks. They do so by targeting specific mRNAs, directly degrading them and/or preventing their translation into proteins. The impaired function of miRNAs results in aberrant gene expression that promotes abnormal cell growth and differentiation. miRNAs, located at fragile sites or cancer associated regions of the genome, act as either tumor suppressor or tumor promoters. miRNAs also play significant role in aging and in various diseases. Despite the fact that profiling of miRNA expression is considered an important tool for diagnostic and therapeutic purposes, such analysis has not yet been adopted in routine clinical care practices. Here, we highlight advances and challenges in research on cancer and aging in relation to miRNAs.