Special Issue "The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2017)

Special Issue Editors

Guest Editor
Dr. Takahiro Ochiya

Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Website | E-Mail
Phone: +81-3-3542-2511
Fax: +81 3 5565 0727
Interests: cancer biology; small rna; intra- and extracellular communication; animal models of human disease; translational research
Guest Editor
Dr. Ryou-u Takahashi

Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Website | E-Mail
Phone: +81 3 3547 5276
Fax: +81 3 5565 0727
Interests: cancer biology; small RNA; cancer stem cells; drug resistance; translational research

Special Issue Information

Dear Colleagues,

MicroRNA (miRNA) is one of the non-coding RNAs that plays important roles in gene regulation, mainly at the post-transcriptional level, and compromises a large family of approximately 20–22 small nucleotide. A number of studies have reported that miRNAs support the maintenance of biological homeostasis, and that aberrant expression of miRNAs are associated with the onset of many diseases, including cancer. This Special Issue of Cancers will firstly introduce the role of miRNAs in tumor development, and will then review their therapeutic potential for cancer therapy. The next several articles will focus on the secreted miRNAs that are packaged into the small endosome-derived vesicles called exosomes, generated from the multiple cell types, including immunocytes and cancer cells. Because secreted miRNAs also play an important role in cell-to-cell communication, they have been investigated as prognostic and diagnostic biomarkers. 

Dr. Takahiro Ochiya
Dr. Ryou-u Takahashi
Guest Editors

Manuscript Submission Information

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Keywords

  • MicroRNA
  • Tumor development
  • Therapeutic approach
  • Circulating microRNA
  • Exosomal microRNA
  • Prognostic and diagnostic markers

Published Papers (8 papers)

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Review

Open AccessFeature PaperReview Roles of microRNAs and RNA-Binding Proteins in the Regulation of Colorectal Cancer Stem Cells
Cancers 2017, 9(10), 143; https://doi.org/10.3390/cancers9100143
Received: 26 September 2017 / Revised: 17 October 2017 / Accepted: 17 October 2017 / Published: 24 October 2017
Cited by 3 | PDF Full-text (753 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer stem cells (CSCs) are responsible for the initiation, progression and metastasis of human colorectal cancers, and have been characterized by the expression of cell surface markers, such as CD44, CD133, CD166 and LGR5. MicroRNAs (miRNAs) are differentially expressed between CSCs and
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Colorectal cancer stem cells (CSCs) are responsible for the initiation, progression and metastasis of human colorectal cancers, and have been characterized by the expression of cell surface markers, such as CD44, CD133, CD166 and LGR5. MicroRNAs (miRNAs) are differentially expressed between CSCs and non-tumorigenic cancer cells, and play important roles in the maintenance and regulation of stem cell properties of CSCs. RNA binding proteins (RBPs) are emerging epigenetic regulators of various RNA processing events, such as splicing, localization, stabilization and translation, and can regulate various types of stem cells. In this review, we summarize current evidences on the roles of miRNA and RBPs in the regulation of colorectal CSCs. Understanding the epigenetic regulation of human colorectal CSCs will help to develop biomarkers for colorectal cancers and to identify targets for CSC-targeting therapies. Full article
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Open AccessFeature PaperReview MicroRNAs as Biomarkers in Colorectal Cancer
Received: 29 June 2017 / Revised: 1 September 2017 / Accepted: 10 September 2017 / Published: 13 September 2017
Cited by 6 | PDF Full-text (235 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRs) are small RNAs that repress mRNA translation, resulting in the degradation of mRNAs and regulation of the expression levels of various genes. Recent studies have shown that aberrant miR expression has a functional role in the initiation and progression of various
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MicroRNAs (miRs) are small RNAs that repress mRNA translation, resulting in the degradation of mRNAs and regulation of the expression levels of various genes. Recent studies have shown that aberrant miR expression has a functional role in the initiation and progression of various malignancies, including colorectal cancer (CRC), which is one of the leading causes of cancer-related death worldwide. miRs have also been shown to have applications as diagnostic, prognostic, and predictive biomarkers because of their high tissue specificity, stability, and altered expression in tumor development. In this report, we examined the role of miRs as biomarkers in CRC through a review of meta-analyses and large-scale analyses having strong statistical confidence in the study outcomes. We also discuss current issues in the clinical application of these miRs. Full article
Open AccessReview Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression
Received: 2 July 2017 / Revised: 1 August 2017 / Accepted: 4 August 2017 / Published: 7 August 2017
Cited by 4 | PDF Full-text (1315 KB) | HTML Full-text | XML Full-text
Abstract
The androgen receptor (AR) plays important roles in prostate cancer development and prostate tumor growth. After binding to androgens, AR functions as a nuclear receptor and translocates to the nucleus to bind to specific AR-binding sites (ARBSs). AR regulates epigenetic factor recruitments to
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The androgen receptor (AR) plays important roles in prostate cancer development and prostate tumor growth. After binding to androgens, AR functions as a nuclear receptor and translocates to the nucleus to bind to specific AR-binding sites (ARBSs). AR regulates epigenetic factor recruitments to activate its downstream signaling. Although androgen deprivation therapy (ADT) is initially useful for prostate cancer patients, most patients eventually show resistance with hormone-refractory prostate cancers (HRPCs) or castration-resistant prostate cancers (CRPCs). Thus, new therapeutic strategies targeting HRPCs/CRPCs should be very important for clinical medicine as well as prostate cancer biology. Past studies have shown that mechanisms such as AR overexpression, hypersensitivity, variants and reprograming are responsible for developing HRPCs/CRPCs. These findings suggest that AR target genes will be major key factors. In this review article, we focus mainly on the androgen-regulated microRNAs (miRNAs) to summarize the contribution of miRNA-mediated pathways for prostate cancer progression. Full article
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Open AccessReview The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas
Received: 31 May 2017 / Revised: 1 July 2017 / Accepted: 3 July 2017 / Published: 10 July 2017
Cited by 2 | PDF Full-text (1045 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that function in gene silencing by post-transcriptional regulation of gene expression. The dysregulation of miRNA plays a pivotal role in cancer tumorigenesis, including the development and progression of gliomas. Their small size, stability and ability
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MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that function in gene silencing by post-transcriptional regulation of gene expression. The dysregulation of miRNA plays a pivotal role in cancer tumorigenesis, including the development and progression of gliomas. Their small size, stability and ability to target multiple oncogenes have simultaneously distinguished miRNAs as attractive candidates for biomarkers and novel therapeutic targets for glioma patients. In this review, we summarize the most frequently cited miRNAs known to contribute to gliomagenesis and progression by regulating the defining hallmarks of gliomas, including angiogenesis, invasion, and cell metabolism. We also discuss their promising potential as prognostic and predictive biomarkers and novel therapeutic targets, in addition to the challenges that must be overcome before their translation from bench to bedside. Full article
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Open AccessReview Specific Depletion of Leukemic Stem Cells: Can MicroRNAs Make the Difference?
Received: 2 May 2017 / Revised: 15 June 2017 / Accepted: 20 June 2017 / Published: 30 June 2017
Cited by 2 | PDF Full-text (1944 KB) | HTML Full-text | XML Full-text
Abstract
For over 40 years the standard treatment for acute myeloid leukemia (AML) patients has been a combination of chemotherapy consisting of cytarabine and an anthracycline such as daunorubicin. This standard treatment results in complete remission (CR) in the majority of AML patients. However,
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For over 40 years the standard treatment for acute myeloid leukemia (AML) patients has been a combination of chemotherapy consisting of cytarabine and an anthracycline such as daunorubicin. This standard treatment results in complete remission (CR) in the majority of AML patients. However, despite these high CR rates, only 30–40% (<60 years) and 10–20% (>60 years) of patients survive five years after diagnosis. The main cause of this treatment failure is insufficient eradication of a subpopulation of chemotherapy resistant leukemic cells with stem cell-like properties, often referred to as “leukemic stem cells” (LSCs). LSCs co-exist in the bone marrow of the AML patient with residual healthy hematopoietic stem cells (HSCs), which are needed to reconstitute the blood after therapy. To prevent relapse, development of additional therapies targeting LSCs, while sparing HSCs, is essential. As LSCs are rare, heterogeneous and dynamic, these cells are extremely difficult to target by single gene therapies. Modulation of miRNAs and consequently the regulation of hundreds of their targets may be the key to successful elimination of resistant LSCs, either by inducing apoptosis or by sensitizing them for chemotherapy. To address the need for specific targeting of LSCs, miRNA expression patterns in highly enriched HSCs, LSCs, and leukemic progenitors, all derived from the same patients’ bone marrow, were determined and differentially expressed miRNAs between LSCs and HSCs and between LSCs and leukemic progenitors were identified. Several of these miRNAs are specifically expressed in LSCs and/or HSCs and associated with AML prognosis and treatment outcome. In this review, we will focus on the expression and function of miRNAs expressed in normal and leukemic stem cells that are residing within the AML bone marrow. Moreover, we will review their possible prospective as specific targets for anti-LSC therapy. Full article
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Open AccessReview Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications
Received: 20 May 2017 / Revised: 16 June 2017 / Accepted: 16 June 2017 / Published: 24 June 2017
Cited by 9 | PDF Full-text (223 KB) | HTML Full-text | XML Full-text
Abstract
Soon after the discovery of microRNAs over 15 years ago, a myriad of research groups around the world sought to develop clinical applications in breast cancer for these short, noncoding, regulatory RNAs. While little of this knowledge has translated into the clinic, the
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Soon after the discovery of microRNAs over 15 years ago, a myriad of research groups around the world sought to develop clinical applications in breast cancer for these short, noncoding, regulatory RNAs. While little of this knowledge has translated into the clinic, the recent research explosion on cell-to-cell communication via exosomes and other extracellular vesicles has rekindled interest in microRNA-based clinical applications. microRNAs appear to be a preferential and important cargo of exosomes in mediating biological effects in recipient cells. This review highlights recent studies on the biology of exosomal microRNAs (exo-miRNAs) and discusses potential clinical applications. From a diagnostic perspective, circulating exo-miRNAs may represent breast cancer cell content and/or tumor microenvironmental reactions to cancer cell growth. Thus, serum or plasma analysis of exo-miRNAs could be useful for early disease detection or for monitoring treatment response and disease progression. From a therapeutic perspective, exo-miRNAs derived from different cell types have been implicated in supporting or restraining tumor growth, conferring drug resistance, and preparing the metastatic niche. Strategies to interfere with the loading or delivery of tumor-promoting exo-miRNAs or to replenish tumor-suppressive miRNAs via exosomal delivery are under investigation. These recent studies provide new hope and opportunities, but study design limitations and technical challenges will need to be overcome before seriously considering clinical application of exo-miRNAs. Full article
Open AccessReview Diagnostic and Therapeutic Potential of MicroRNAs in Lung Cancer
Received: 8 March 2017 / Revised: 13 April 2017 / Accepted: 8 May 2017 / Published: 9 May 2017
Cited by 15 | PDF Full-text (237 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer is the leading cause of deaths resulting from cancer owing to late diagnosis and limited treatment intervention. MicroRNAs are short, non-coding RNA molecules that regulate gene expression post-transcriptionally by translational repression or target messenger RNA degradation. Accumulating evidence suggests various roles
[...] Read more.
Lung cancer is the leading cause of deaths resulting from cancer owing to late diagnosis and limited treatment intervention. MicroRNAs are short, non-coding RNA molecules that regulate gene expression post-transcriptionally by translational repression or target messenger RNA degradation. Accumulating evidence suggests various roles for microRNAs, including development and progression of lung cancers. Because microRNAs are degraded to a much lesser extent in formalin-fixed paraffin-embedded specimens and are present not only in tumor tissues but also in body fluids, there is an increased potential in microRNA analyses for cancer research. In this review, recent studies of microRNA are introduced and briefly summarized, with a focus on the association of microRNAs with histological subtypes, genetic driver alterations, therapeutically-targeted molecules, and carcinogens. The reported circulating microRNA signature for the early detection of lung cancer and the implications of microRNAs as the modulators of tumor immune response are also introduced. Full article
Open AccessReview Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells
Received: 27 February 2017 / Revised: 14 April 2017 / Accepted: 18 April 2017 / Published: 21 April 2017
Cited by 22 | PDF Full-text (921 KB) | HTML Full-text | XML Full-text
Abstract
Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance
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Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure. One type of ncRNA, called long non-coding RNAs (lncRNAs), has become increasingly recognized as being both highly dysregulated in cancer and to play a variety of different roles in tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have been associated with the EMT process in cancer and the variety of molecular mechanisms and signalling pathways through which they regulate EMT, and finally discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug resistance and the cancer stem cell phenotype. Full article
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