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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

miRNA biogenesis process. A schematic representation of canonical miRNA biogenesis pathway. Each miRNA is transcribed by RNA polymerase II (pri-miRNA) from genomic DNA within the nucleus; pri-miRNA is recognized by Drosha-DGCR8 and processed to pre-miRNA. Pre-miRNA is exported to the cytoplasm by exportin 5 (XPO5), where it is processed and cleaved by DICER complex to a double strand miRNA (miRNA*-miRNA). The duplex is cleaved, and only the mature miRNA is loaded into the RISC complex. The degree of homology of the miRNA “seed” to the 3′ UTR target sequence of the mRNA determines the mRNA translational repression or degradation.
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Figure 1: miRNA biogenesis process. A schematic representation of canonical miRNA biogenesis pathway. Each miRNA is transcribed by RNA polymerase II (pri-miRNA) from genomic DNA within the nucleus; pri-miRNA is recognized by Drosha-DGCR8 and processed to pre-miRNA. Pre-miRNA is exported to the cytoplasm by exportin 5 (XPO5), where it is processed and cleaved by DICER complex to a double strand miRNA (miRNA*-miRNA). The duplex is cleaved, and only the mature miRNA is loaded into the RISC complex. The degree of homology of the miRNA “seed” to the 3′ UTR target sequence of the mRNA determines the mRNA translational repression or degradation.

Mentions: miRNAs are transcribed from individual genes containing their own promoter, or intragenically from spliced portions of protein-coding genes 24. Like protein-coding genes, miRNAs with their own promoters are almost exclusively transcribed by RNA polymerase II in a primary transcript called pri-miRNA 24 (Figure 1). This long transcript contains a 7-methylguanosine cap at the 5′ end, a 3′ poly-(A) tail, and sometimes also introns. To be processed, pri-miRNAs are recognized by Drosha ribonuclease and its partner, the double-stranded RNA binding protein DGCR8, through interaction with a stem-loop structure within the miRNA in which the sequences are not perfectly complementary 25, 26. Processing of pri-miRNAs gives rise to precursor miRNAs (pre-miRNAs) of approximately 70 nucleotides 24 (Figure 1). Some intronic miRNAs, called mirtrons, could bypass Drosha processing and use the splicing machinery to generate pre-miRNAs 24. The generated pre-miRNAs are then exported from the nucleus to the cytoplasm by exportin 5 (XPO5) 27-29, where they are cleaved by the RNase III enzyme Dicer 1 in union with transactivation-responsive RNA-binding protein 2 (TARBP2) and AGO2 (DICER complex). The processing generates a double-stranded miRNA-miRNA* duplex 30. The 2 strands are then separated: the mature miRNA (the guide strand) is incorporated into the RNA-induced silencing complex (RISC), whereas the passage miRNA* strand can be loaded in the RISC as well or degraded 31-33. The mature miRNA guides the AGO protein of the RISC to the complementary mRNA sequence on the target to repress its expression 24 (Figure 1).


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

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

miRNA biogenesis process. A schematic representation of canonical miRNA biogenesis pathway. Each miRNA is transcribed by RNA polymerase II (pri-miRNA) from genomic DNA within the nucleus; pri-miRNA is recognized by Drosha-DGCR8 and processed to pre-miRNA. Pre-miRNA is exported to the cytoplasm by exportin 5 (XPO5), where it is processed and cleaved by DICER complex to a double strand miRNA (miRNA*-miRNA). The duplex is cleaved, and only the mature miRNA is loaded into the RISC complex. The degree of homology of the miRNA “seed” to the 3′ UTR target sequence of the mRNA determines the mRNA translational repression or degradation.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4508501&req=5

Figure 1: miRNA biogenesis process. A schematic representation of canonical miRNA biogenesis pathway. Each miRNA is transcribed by RNA polymerase II (pri-miRNA) from genomic DNA within the nucleus; pri-miRNA is recognized by Drosha-DGCR8 and processed to pre-miRNA. Pre-miRNA is exported to the cytoplasm by exportin 5 (XPO5), where it is processed and cleaved by DICER complex to a double strand miRNA (miRNA*-miRNA). The duplex is cleaved, and only the mature miRNA is loaded into the RISC complex. The degree of homology of the miRNA “seed” to the 3′ UTR target sequence of the mRNA determines the mRNA translational repression or degradation.
Mentions: miRNAs are transcribed from individual genes containing their own promoter, or intragenically from spliced portions of protein-coding genes 24. Like protein-coding genes, miRNAs with their own promoters are almost exclusively transcribed by RNA polymerase II in a primary transcript called pri-miRNA 24 (Figure 1). This long transcript contains a 7-methylguanosine cap at the 5′ end, a 3′ poly-(A) tail, and sometimes also introns. To be processed, pri-miRNAs are recognized by Drosha ribonuclease and its partner, the double-stranded RNA binding protein DGCR8, through interaction with a stem-loop structure within the miRNA in which the sequences are not perfectly complementary 25, 26. Processing of pri-miRNAs gives rise to precursor miRNAs (pre-miRNAs) of approximately 70 nucleotides 24 (Figure 1). Some intronic miRNAs, called mirtrons, could bypass Drosha processing and use the splicing machinery to generate pre-miRNAs 24. The generated pre-miRNAs are then exported from the nucleus to the cytoplasm by exportin 5 (XPO5) 27-29, where they are cleaved by the RNase III enzyme Dicer 1 in union with transactivation-responsive RNA-binding protein 2 (TARBP2) and AGO2 (DICER complex). The processing generates a double-stranded miRNA-miRNA* duplex 30. The 2 strands are then separated: the mature miRNA (the guide strand) is incorporated into the RNA-induced silencing complex (RISC), whereas the passage miRNA* strand can be loaded in the RISC as well or degraded 31-33. The mature miRNA guides the AGO protein of the RISC to the complementary mRNA sequence on the target to repress its expression 24 (Figure 1).

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