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Open AccessFeature PaperReview

Roles of microRNAs and RNA-Binding Proteins in the Regulation of Colorectal Cancer Stem Cells

by Junko Mukohyama, Yohei Shimono, Hironobu Minami, Yoshihiro Kakeji and Akira Suzuki

Cancers 2017, 9(10), 143; https://doi.org/10.3390/cancers9100143 - 24 Oct 2017

Cited by 28 | Viewed by 7215

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 [...] Read more.

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

(This article belongs to the Special Issue The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential)

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Open AccessFeature PaperReview

MicroRNAs as Biomarkers in Colorectal Cancer

by Takaaki Masuda, Naoki Hayashi, Yosuke Kuroda, Shuhei Ito, Hidetoshi Eguchi and Koshi Mimori

Cancers 2017, 9(9), 124; https://doi.org/10.3390/cancers9090124 - 13 Sep 2017

Cited by 89 | Viewed by 6439

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 [...] Read more.

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

(This article belongs to the Special Issue The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential)

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Open AccessReview

Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression

by Ken-ichi Takayama, Aya Misawa and Satoshi Inoue

Cancers 2017, 9(8), 102; https://doi.org/10.3390/cancers9080102 - 07 Aug 2017

Cited by 32 | Viewed by 5960

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 [...] Read more.

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

(This article belongs to the Special Issue The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential)

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Open AccessReview

The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas

by Sasha Beyer, Jessica Fleming, Wei Meng, Rajbir Singh, S. Jaharul Haque and Arnab Chakravarti

Cancers 2017, 9(7), 85; https://doi.org/10.3390/cancers9070085 - 10 Jul 2017

Cited by 48 | Viewed by 7036

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 [...] Read more.

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

(This article belongs to the Special Issue The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential)

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Open AccessReview

Specific Depletion of Leukemic Stem Cells: Can MicroRNAs Make the Difference?

by Tania Martiáñez Canales, David C. De Leeuw, Eline Vermue, Gert J. Ossenkoppele and Linda Smit

Cancers 2017, 9(7), 74; https://doi.org/10.3390/cancers9070074 - 30 Jun 2017

Cited by 6 | Viewed by 8449

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, [...] Read more.

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

(This article belongs to the Special Issue The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential)

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Open AccessReview

Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications

by Lorenzo F. Sempere, Jessica Keto and Muller Fabbri

Cancers 2017, 9(7), 71; https://doi.org/10.3390/cancers9070071 - 24 Jun 2017

Cited by 77 | Viewed by 8168

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 [...] Read more.

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

(This article belongs to the Special Issue The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential)

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Open AccessReview

Diagnostic and Therapeutic Potential of MicroRNAs in Lung Cancer

by Kentaro Inamura

Cancers 2017, 9(5), 49; https://doi.org/10.3390/cancers9050049 - 09 May 2017

Cited by 57 | Viewed by 6511

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

(This article belongs to the Special Issue The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential)

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Open AccessReview

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

by Richard Heery, Stephen P. Finn, Sinead Cuffe and Steven G. Gray

Cancers 2017, 9(4), 38; https://doi.org/10.3390/cancers9040038 - 21 Apr 2017

Cited by 160 | Viewed by 11253

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 [...] Read more.

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

(This article belongs to the Special Issue The Roles of microRNA in Tumor Initiation and Development: Diagnostic and Therapeutic Potential)

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