Abstract
MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that post-transcriptionally inhibit gene expression. Many miRNAs have been implicated in several human cancers, including breast cancer. Here we describe the association between altered miRNA signatures and breast cancer tumorigenesis and metastasis. The loss of several tumor suppressor miRNAs (miR-206, miR-17-5p, miR-125a, miR-125b, miR-200, let-7, miR-34 and miR-31) and the overexpression of certain oncogenic miRNAs (miR-21, miR-155, miR-10b, miR-373 and miR-520c) have been observed in many breast cancers. The gene networks orchestrated by these miRNAs are still largely unknown, although key targets have been identified that may contribute to the disease phenotype. Here we report how the observed perturbations in miRNA expression profiles may lead to disruption of key pathways involved in breast cancer.
Highlights
MicroRNAs are an evolutionarily conserved class of small, approximately 22-nucleotide non-coding RNAs that decrease gene expression post-transcriptionally in a sequence-specific manner
Most miRNAs are transcribed in the nucleus by RNA polymerase II as long primary transcripts that undergo processing by Drosha and DGCR8, resulting in an approximately 70-nucleotide stem-loop RNA
To further elucidate the molecular mechanisms that regulate the function of miR-21, proteomic analysis of the above-mentioned xenograft tumors revealed that the tumor suppressor protein tropomyosin 1 (TPM1), which is known to be downregulated in breast cancer epithelial cell lines, was a target of miR-21 [64]
Summary
MicroRNAs (miRNAs) are an evolutionarily conserved class of small, approximately 22-nucleotide non-coding RNAs that decrease gene expression post-transcriptionally in a sequence-specific manner. These two miRNAs are potential tumor suppressors and their overexpression in SKBR3 cells (a HER2-dependent human breast cancer cell line) suppresses HER2 and HER3 mRNA and protein levels, leading to a reduction in anchorage-dependent growth, cell motility, and invasiveness [41].
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