Potential Role of miR-21 in Breast Cancer Diagnosis and Therapy - Abstract
MicroRNAs are a large family of short non-coding RNA molecules involved in the regulation of gene expression. MIRN21 gene residing on chromosome 17 is linked to cancer initiation, progression and therapeutic response.
The mature miRNA is 22 nucleotides long, forms one strand of the RNA duplex which is incorporated into a protein complex, targeting a partially complementary target mRNA. miRNAs act not only within cells of origin but are transported into the bloodstream and is taken up by recipient cells and processed into mature miRNA.
miRNA expression signatures are associated not only with specific tumor subtypes but in clinical outcomes as well. Deregulation of miRNA in cancer takes place by transcriptional deregulation, epigenetic alterations or mutation.
MiR-21 are considered an ‘oncomir’ since it could suppress the actions of several apoptotic and tumor suppressor genes, leading to tumor cell proliferation, inhibition of apoptosis, migration, invasion, angiogenesis, and metastasis. The reduction or deletion of a miRNA, because of defects of its biogenesis, leads to tumor formation. The amplification or over-expression of a miRNA that has an oncogenic role would also lead to tumor formation. Clinical characteristics of breast cancer associated with increased miR-21 expression level were significantly correlated with higher tumor grade, increased tumor size, lymph node involvement, lympho-vascular invasion and in patients with poor prognosis.
Quantification of microRNAs can be used to predict the prognosis, clinical behavior of the tumor, and monitor the response to treatment. Altered serum or tissue microRNAs expression has served as a useful potential non-invasive biomarker for cancer detection, evaluation, and follow-up. The level of miR-21 expression is significantly associated with clinicopathological factors and the prognosis of tumor patients.
Modulation of miR-21 expression as potential cancer therapy was investigated in various cancer types. The inhibition of miRNAs, using antisense oligonucleotides (ASOs) and artificial oligonucleotides constructed on a peptide-like backbone are effective techniques for investigating miRNA functions and targets. Therapeutic delivery, using specific antisense oligonucleotide of miR-21 may still be beneficial for a large number of cancers for which no cure is available. Inhibitors of miR-21 may also function as effective approaches for reversing drug resistance in cancer cells.