Limits...
Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers

View Article: PubMed Central - PubMed

ABSTRACT

Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC.

No MeSH data available.


Related in: MedlinePlus

Role of deregulated miRs in BTC and their potential use as biomarkers. (a) Deregulation of miR expression in BTC tissue versus healthy controls results in unfavourable clinicopathological characteristics as well as poor outcome (upper part). Validated direct targets of deregulated miRs in BTC model systems include known tumor suppressors and oncogenes. Overexpression of oncogenic miRs results in aberrant downregulation of target tumor suppressors, whereas underexpression of tumor suppressor miRs results in insufficient negative transcriptional control of oncogenes (marked as red “X”), leading to their upregulation. Both of these events eventually cause diverse oncogenic effects (lower part). Figure based on Table 1. (b) Summary of distinguishing power of individual miRs regarding their use as potential biomarkers. The area under curve values from individual studies (reference numbers in square brackets; for details, see Table 2) indicate the quality of the respective miR as a biomarker (between 0.5 and max. 1.0), compared to CA19-9 as a conventional marker. Green boxes indicate miRs for which deregulation in BTC tissue as well as the use as a biomarker for BTC has been investigated. ‡: from plasma; ‡‡: from serum; ‡‡‡: from urine. For full gene names, see Abbreviations. BBD: benign biliary disease; BTC: biliary tract cancer; EMT: epithelial-mesenchymal transition; miR: microRNA; PSC: primary sclerosing cholangitis.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5120202&req=5

fig1: Role of deregulated miRs in BTC and their potential use as biomarkers. (a) Deregulation of miR expression in BTC tissue versus healthy controls results in unfavourable clinicopathological characteristics as well as poor outcome (upper part). Validated direct targets of deregulated miRs in BTC model systems include known tumor suppressors and oncogenes. Overexpression of oncogenic miRs results in aberrant downregulation of target tumor suppressors, whereas underexpression of tumor suppressor miRs results in insufficient negative transcriptional control of oncogenes (marked as red “X”), leading to their upregulation. Both of these events eventually cause diverse oncogenic effects (lower part). Figure based on Table 1. (b) Summary of distinguishing power of individual miRs regarding their use as potential biomarkers. The area under curve values from individual studies (reference numbers in square brackets; for details, see Table 2) indicate the quality of the respective miR as a biomarker (between 0.5 and max. 1.0), compared to CA19-9 as a conventional marker. Green boxes indicate miRs for which deregulation in BTC tissue as well as the use as a biomarker for BTC has been investigated. ‡: from plasma; ‡‡: from serum; ‡‡‡: from urine. For full gene names, see Abbreviations. BBD: benign biliary disease; BTC: biliary tract cancer; EMT: epithelial-mesenchymal transition; miR: microRNA; PSC: primary sclerosing cholangitis.

Mentions: MicroRNAs are of great scientific and clinical interest, as it becomes more and more clear that this noncoding RNA species is a major factor in cancer diseases [23]. Their sheer number combined with their ability to potentially target multiple protein-coding transcripts gives an idea of the overall regulatory power of miRNAs [20]. For BTC, not only might miRNAs constitute new therapeutic targets themselves but also their function helps shed more light on the cellular and pathologic processes contributing to BTC carcinogenesis. As summarized in this review and in Figure 1(a), identification of direct targets of deregulated miRNAs in BTC can provide valuable knowledge about functional associations and new starting points for therapeutic strategies (Table 1). As one intensively investigated example, miRNA-21 was found to be frequently deregulated in BTC samples with poor clinicopathological features (Table 1). By directly promoting tumor growth and aggressiveness via direct transcriptional suppression of known tumor suppressor genes, miRNA-21 acts as a potent oncogenic miRNA.


Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers
Role of deregulated miRs in BTC and their potential use as biomarkers. (a) Deregulation of miR expression in BTC tissue versus healthy controls results in unfavourable clinicopathological characteristics as well as poor outcome (upper part). Validated direct targets of deregulated miRs in BTC model systems include known tumor suppressors and oncogenes. Overexpression of oncogenic miRs results in aberrant downregulation of target tumor suppressors, whereas underexpression of tumor suppressor miRs results in insufficient negative transcriptional control of oncogenes (marked as red “X”), leading to their upregulation. Both of these events eventually cause diverse oncogenic effects (lower part). Figure based on Table 1. (b) Summary of distinguishing power of individual miRs regarding their use as potential biomarkers. The area under curve values from individual studies (reference numbers in square brackets; for details, see Table 2) indicate the quality of the respective miR as a biomarker (between 0.5 and max. 1.0), compared to CA19-9 as a conventional marker. Green boxes indicate miRs for which deregulation in BTC tissue as well as the use as a biomarker for BTC has been investigated. ‡: from plasma; ‡‡: from serum; ‡‡‡: from urine. For full gene names, see Abbreviations. BBD: benign biliary disease; BTC: biliary tract cancer; EMT: epithelial-mesenchymal transition; miR: microRNA; PSC: primary sclerosing cholangitis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120202&req=5

fig1: Role of deregulated miRs in BTC and their potential use as biomarkers. (a) Deregulation of miR expression in BTC tissue versus healthy controls results in unfavourable clinicopathological characteristics as well as poor outcome (upper part). Validated direct targets of deregulated miRs in BTC model systems include known tumor suppressors and oncogenes. Overexpression of oncogenic miRs results in aberrant downregulation of target tumor suppressors, whereas underexpression of tumor suppressor miRs results in insufficient negative transcriptional control of oncogenes (marked as red “X”), leading to their upregulation. Both of these events eventually cause diverse oncogenic effects (lower part). Figure based on Table 1. (b) Summary of distinguishing power of individual miRs regarding their use as potential biomarkers. The area under curve values from individual studies (reference numbers in square brackets; for details, see Table 2) indicate the quality of the respective miR as a biomarker (between 0.5 and max. 1.0), compared to CA19-9 as a conventional marker. Green boxes indicate miRs for which deregulation in BTC tissue as well as the use as a biomarker for BTC has been investigated. ‡: from plasma; ‡‡: from serum; ‡‡‡: from urine. For full gene names, see Abbreviations. BBD: benign biliary disease; BTC: biliary tract cancer; EMT: epithelial-mesenchymal transition; miR: microRNA; PSC: primary sclerosing cholangitis.
Mentions: MicroRNAs are of great scientific and clinical interest, as it becomes more and more clear that this noncoding RNA species is a major factor in cancer diseases [23]. Their sheer number combined with their ability to potentially target multiple protein-coding transcripts gives an idea of the overall regulatory power of miRNAs [20]. For BTC, not only might miRNAs constitute new therapeutic targets themselves but also their function helps shed more light on the cellular and pathologic processes contributing to BTC carcinogenesis. As summarized in this review and in Figure 1(a), identification of direct targets of deregulated miRNAs in BTC can provide valuable knowledge about functional associations and new starting points for therapeutic strategies (Table 1). As one intensively investigated example, miRNA-21 was found to be frequently deregulated in BTC samples with poor clinicopathological features (Table 1). By directly promoting tumor growth and aggressiveness via direct transcriptional suppression of known tumor suppressor genes, miRNA-21 acts as a potent oncogenic miRNA.

View Article: PubMed Central - PubMed

ABSTRACT

Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC.

No MeSH data available.


Related in: MedlinePlus