MicroRNAs (miRNAs) are small RNAs that have emerged as potent regulators of the target genes messenger RNAs expression in the response of cell to both physiological and pathophysiological conditions. Reflecting pathological processes today, miRNAs are widely validated for their potential role in diagnostic, prognostic and novel therapeutic targeting for cancerous and other diseases. miR-155 is considered as a typical multifunctional miRNA including its role as oncomiR (cancer-associated miRNA). Expression of miR-155 is upregulated in cells with high proliferative activity and decreased apoptotic capability. It belongs to cluster of well-characterized tumor associated miRNAs detectable also in the peripheral blood. In this review we summarize the principles of miR-155 host gene expressional regulation, as well as its role in regulation of the target genes mRNAs. Altered expression of miR-155 has been described in multiple cancerous and other diseases, reflecting staging, progress and treatment outcomes. Therefore, miR-155 became a potential biomarker and candidate for clinical utilization as predictor of the presence of cancer, its staging and prognosis.

Deregulated expression of microRNAs has the oncogenic or tumor suppressor function in cancer. Since miRNAs in plasma are highly stable, their quantification could contribute to more precise cancer diagnosis, prognosis and therapy prediction. We have quantified expression of seven oncomiRs, namely miR-17/92 cluster (miR-17, miR-18a, miR-19a and miR-20a), miR-21, miR-27a and miR-155, in plasma of 137 breast cancer (BC) patients. We detected down-regulation of six miRNAs in patients with invasive BC compared to controls; however, only miR-20a and miR-27a down-regulations were statistically significant. Comparing miRNA expression between early and advanced stages of BC, we observed statistically significant decrease of miR-17 and miR-19a. We identified down-regulation of miR-17 and miR-20a in patients with clinical parameters of advanced BC (lymph node metastasis, tumor grade 3, circulating tumor cells, higher Ki-67-related proliferation, hormone receptor negativity and HER2 amplification), when compared to controls. Moreover, decreased level of miR-17 was found from low to high grade. Therefore, miR-17 could represent an indicator of advanced BC. Down-regulated miR-27a expression levels were observed in all clinical categories regardless of tumor progression. Hence, miR-27a could be used as a potential diagnostic marker for BC. Our data indicates that any changes in miRNA expression levels in BC patients in comparison to controls could be highly useful for cancer-associated pathology discrimination. Moreover, dynamics of miRNA expression changes could be used for BC progression monitoring.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cells carrying Philadelphia (Ph) chromosome and the oncogenic BCR-ABL1 fusion gene. microRNAs (miRNAs) belong to hematopoiesis transcription regulators and their deregulated expression associates with pathogenesis of CML. The current study assesses and validates expression profiles of selected oncogenic and tumor suppressing miRNAs that are associated with different imatinib mesylate (IM) response in CML patients carrying rare BCR-ABL variants. Microarray analysis has identified different expression of 70 miRNAs (46 up- and 24 down-regulated) when compared IM-resistant with IM-responsive patients carrying Ph chromosome. Significantly up-regulated expression of oncogenic miRNAs (miR-17, miR-18a, miR-20a, miR-21, miR-27a and miR-155) and significantly down-regulated expression of tumor supressing mRNAs (let-7d, miR-205, miR-320, miR-451 and miR-574) in IM-resistant compared to IM-responsive patients was confirmed and validated by qRT-PCR. This study confirms the involvement of the selected oncogenic and tumor suppressing miRNAs in CML pathogenesis and IM response and suggests that these miRNAs could be suitable biomarkers for differential diagnosis of CML patients carrying rare BCR-ABL transcripts, as well as for prediction of their IM response and therapy outcome.

Breast cancer (BC) including its progression into bone metastasis is a complex process involving changes in gene expression and function of both, microRNAs (miRNAs) and their target genes. Deregulation of miRNAs has been described as a crucial factor responsible for the initiation and progression of BC, and specific miRNA expression profiles have been found to be associated with particular disease states, histological tumor types, and BRCA1/2 or HER status. BRCA1 tumor suppressor is involved in DNA damage response and repair and epigenetically controls miR-155 expression and its pre-cancerous potential. MiR-155 targets 3´UTR region of multiple components of the pro-oncogenic signaling cascades, including FOXO3a tumor suppressor and RUNX2 transcription factor regulating metastatic potential in BC. We employed qRT-PCR to determine expression level and examine possible regulatory role of selected miRNAs (miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-27a and miR-155) and their impact on expression modulation of FOXO3a and RUNX2 in peripheral blood mononuclear cells (PBMCs) in healthy individuals, in women carrying BRCA1 mutations with no disease manifestation, in women carrying BRCA1 mutations after tumor resection and therapy and in women with BC of unknown BRCA1 status in acute stage before tumor resection. Our results showed significant increase of miR-17, miR-19a, miR-21, miR-27, miR-155 and RUNX2 expression in PBMCs in BRCA1 patients and patients in acute stage, while FOXO3a expression was significantly decreased in these patients. MiR-18a and miR-20a expression was not affected. We propose that expressional changes reported in this study could provide significant additive information for early BC diagnosis, disease development prediction and therapy outcome monitoring.