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MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer.

Bertoli G, Cava C, Castiglioni I - Theranostics (2015)

Bottom Line: Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability.In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC.New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Milan, Italy.

ABSTRACT
Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

No MeSH data available.


Related in: MedlinePlus

Contribution of transcription to miRNA level alteration in cancer. Several transcription factors are able to control the level of expression of miRNAs. In particular, as described in the text, SMAD, Myc, ATM, BRCA1/2 and p53 influence miRNA transcription. P53 can regulate onco-suppressor miRNAs, which are involved in the control of p53 turnover. SMAD, ATM, BRCA1/2 and Myc could influence the transcription levels of miRNAs involved in cell plasticity, cell proliferation and survival, and cell invasion control. Moreover, SMAD is also involved in miRNA processing, by Drosha expression levels control. Ex: example of miRNA regulated by transcription factors.
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Figure 4: Contribution of transcription to miRNA level alteration in cancer. Several transcription factors are able to control the level of expression of miRNAs. In particular, as described in the text, SMAD, Myc, ATM, BRCA1/2 and p53 influence miRNA transcription. P53 can regulate onco-suppressor miRNAs, which are involved in the control of p53 turnover. SMAD, ATM, BRCA1/2 and Myc could influence the transcription levels of miRNAs involved in cell plasticity, cell proliferation and survival, and cell invasion control. Moreover, SMAD is also involved in miRNA processing, by Drosha expression levels control. Ex: example of miRNA regulated by transcription factors.

Mentions: 4. Transcriptional repression by other upstream proteins (Figure 4). A plethora of transcription factors can influence the expression levels of a single miRNA. Several lines of evidence suggest that miRNAs and transcription factors work cooperatively. miRNAs are involved in the functional feedback loop, in which transcription factors influence miRNA expression levels and vice versa 92-94. Thus, tumorigenic miRNA expression alterations could be due to the activity of tumor-related transcription factors, such as SMAD 90, 95, p53 protein family (p53, p63, and p73) 96, ataxia telangiectasia mutated (ATM) 97, and Myc 98. In BC, the BC 1, early onset (BRCA1) transcription factor 99 and the epidermal growth factor receptor (EGFR/HER1), a hypoxic transcription factor involved in the regulation of the RISC 100, are able to inhibit miRNA maturation, thus enhancing cell survival and invasiveness.


MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer.

Bertoli G, Cava C, Castiglioni I - Theranostics (2015)

Contribution of transcription to miRNA level alteration in cancer. Several transcription factors are able to control the level of expression of miRNAs. In particular, as described in the text, SMAD, Myc, ATM, BRCA1/2 and p53 influence miRNA transcription. P53 can regulate onco-suppressor miRNAs, which are involved in the control of p53 turnover. SMAD, ATM, BRCA1/2 and Myc could influence the transcription levels of miRNAs involved in cell plasticity, cell proliferation and survival, and cell invasion control. Moreover, SMAD is also involved in miRNA processing, by Drosha expression levels control. Ex: example of miRNA regulated by transcription factors.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4508501&req=5

Figure 4: Contribution of transcription to miRNA level alteration in cancer. Several transcription factors are able to control the level of expression of miRNAs. In particular, as described in the text, SMAD, Myc, ATM, BRCA1/2 and p53 influence miRNA transcription. P53 can regulate onco-suppressor miRNAs, which are involved in the control of p53 turnover. SMAD, ATM, BRCA1/2 and Myc could influence the transcription levels of miRNAs involved in cell plasticity, cell proliferation and survival, and cell invasion control. Moreover, SMAD is also involved in miRNA processing, by Drosha expression levels control. Ex: example of miRNA regulated by transcription factors.
Mentions: 4. Transcriptional repression by other upstream proteins (Figure 4). A plethora of transcription factors can influence the expression levels of a single miRNA. Several lines of evidence suggest that miRNAs and transcription factors work cooperatively. miRNAs are involved in the functional feedback loop, in which transcription factors influence miRNA expression levels and vice versa 92-94. Thus, tumorigenic miRNA expression alterations could be due to the activity of tumor-related transcription factors, such as SMAD 90, 95, p53 protein family (p53, p63, and p73) 96, ataxia telangiectasia mutated (ATM) 97, and Myc 98. In BC, the BC 1, early onset (BRCA1) transcription factor 99 and the epidermal growth factor receptor (EGFR/HER1), a hypoxic transcription factor involved in the regulation of the RISC 100, are able to inhibit miRNA maturation, thus enhancing cell survival and invasiveness.

Bottom Line: Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability.In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC.New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Milan, Italy.

ABSTRACT
Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

No MeSH data available.


Related in: MedlinePlus