The role of microRNAs in the regulation of cancer stem cells

Takahashi, Ryou U.; Mitsuya, Hiroaki; Ochiya, Takahiro

doi:10.3389/fgene.2013.00295

Cited by 136 publications

(129 citation statements)

References 132 publications

(173 reference statements)

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“…Since microRNA (miRNA) discovery in the early 1990s (Arasu et al 1991;Lee et al 1993), it has become evident that post-transcriptional gene regulation by miRNAs is involved in most biological processes (Grosshans and Slack 2002;Friedman et al 2009;Ameres and Zamore 2013;Sun and Lai 2013;Takahashi et al 2014). The latest miRBase release contains 24,521 experimentally validated miRNA genes from 206 species (Kozomara and Griffiths-Jones 2014).…”

Section: Introductionmentioning

confidence: 99%

Nucleotide specificity of the human terminal nucleotidyltransferase Gld2 (TUT2)

Chung

Heinemann

2016

RNA

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The nontemplated addition of single or multiple nucleotides to RNA transcripts is an efficient means to control RNA stability and processing. Cytoplasmic RNA adenylation and the less well-known uridylation are post-transcriptional mechanisms regulating RNA maturation, activity, and degradation. Gld2 is a member of the noncanonical poly(A) polymerases, which include enzymes with varying nucleotide specificity, ranging from strictly ATP to ambiguous to exclusive UTP adding enzymes. Human Gld2 has been associated with transcript stabilizing miRNA monoadenylation and cytoplasmic mRNA polyadenylation. Most recent data have uncovered an unexpected miRNA uridylation activity, which promotes miRNA maturation. These conflicting data raise the question of Gld2 nucleotide specificity. Here, we biochemically characterized human Gld2 and demonstrated that it is a bona fide adenylyltransferase with only weak activity toward other nucleotides. Despite its sequence similarity with uridylyltransferases (TUT4, TUT7), Gld2 displays an 83-fold preference of ATP over UTP. Gld2 is a promiscuous enzyme, with activity toward miRNA, pre-miRNA, and polyadenylated RNA substrates. Apo-Gld2 activity is restricted to adding single nucleotides and processivity likely relies on additional RNA-binding proteins. A phylogeny of the PAP/TUTase superfamily suggests that uridylyltransferases, which are derived from distinct adenylyltransferase ancestors, arose multiple times during evolution via insertion of an active site histidine. A corresponding histidine insertion into the Gld2 active site alters substrate specificity from ATP to UTP.

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Section: Introductionmentioning

confidence: 99%

Nucleotide specificity of the human terminal nucleotidyltransferase Gld2 (TUT2)

Chung

Heinemann

2016

RNA

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“…Inmultivariate analysis, higher expression of miR-30c was associated with benefit from first line tamoxifen monotherapy and longer progression-free survival [93,94]. Mostert et al, stated that cancer-initiating cells or CSCs were responsible for tumor development and progression.…”

Section: The Mirnas and Breast Cancermentioning

confidence: 99%

“…Mostert et al, stated that cancer-initiating cells or CSCs were responsible for tumor development and progression. These cells share a number of different biological properties with the normal somatic stem cells including the capacity for asymmetric cell division and the ability to efflux the small compounds [72,93]; however, the CSCs vary from normal stem cells in their tumor seeding and abilities of metastasis. In addition, the phenotypic plasticity of the CSCs, which is their capacity to distinguish into non-CSCs, is thought to be an important factor to prevent tumor malignancy [95].…”

Section: The Mirnas and Breast Cancermentioning

confidence: 99%

Diagnostic utility of miRNAs in cancer A review

Jalaeikhoo

Zokaasadi

Rajaeinejad

et al. 2018

Multidiscip Cancer Investig

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Cancer is the one of most prevalent and leading causes of death in the world. Current advancements in technology improve the understanding of the pathogenesis and pathology of cancers. But, due to enlarging mortality rates, poor prognosis, and lacunae in clinical early predictive biomarkers provide an important momentum to investigate novel early diagnostic/prognostic markers and specific targets for cancers therapeutics sufficiently sensitive to cancers. Recently, the emerging small noncoding microRNAs (miRNAs) are suggested as important and critical regulators in the oncogenesis pathways and serve as precise and useful early clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis and recent miRNA expression studies in tumors yield promising results. However, establishing miRNA expression in the blood circulation, cell-free as noninvasive marker, has advantages over determination of tumor in primary tissue. A better understanding of the involvement of this class of molecular markers in carcinogenesis could provide new insights into the mechanisms in the development of tumor and could be helpful to identify new specific novel early powerful markers for the early detection of cancer. The current review study aimed at summarizing the recent research studies supporting the utility of miRNAs as novel early diagnostic and prognostic tools, thus potentially illuminating future treatment strategies for cancers, which indicates the feasibility and clinical applications and the importance of miRNAs in cancer for researchers and clinical diagnostic centers.

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“…Several miRNAs regulate CSCs properties, including self-renewal ability, tumorigenicity and drug resistance (120)(121)(122)(123). CSCs have generally high levels of oncogenic miRNAs and low levels of tumor suppressive miRNAs (122).…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Cancer stem cells as a potential therapeutic target in thyroid carcinoma

Vicari¹,

Colarossi²,

Giuffrida³

et al. 2016

Oncology Letters

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Abstract.A number of studies have indicated that tumor growth and proliferation is dependent on a small subset of cells, defined as cancer stem cells (CSCs). CSCs have the capability to self-renew, and are involved with cancer propagation, relapse and metastatic dissemination. CSCs have been isolated from numerous tissues, including normal and cancerous thyroid tissue. A regulatory network of signaling pathways and microRNAs (miRNAs) control the properties of CSCs. Differentiated thyroid carcinoma is the most common type of endocrine cancer, with an increasing incidence. Anaplastic thyroid carcinoma is the most rare type of endocrine cancer; however, it also exhibits the highest mortality rate among thyroid malignancies, with an extremely short survival time. Thyroid CSCs are invasive and highly resistant to conventional therapies, including radiotherapy and chemotherapy, which results in disease relapse even when the primary lesion has been eradicated. Therefore, targeting thyroid CSCs may represent an effective treatment strategy against aggressive neoplasms, including recurrent and radioresistant tumors. The present review summarizes the current literature regarding thyroid CSCs and discusses therapeutic strategies that target these cells, with a focus on the function of self-renewal pathways and miRNAs. Elucidation of the mechanisms that regulate CSC growth and survival may improve novel therapeutic approaches for treatment-resistant thyroid cancers.

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The role of microRNAs in the regulation of cancer stem cells

Cited by 136 publications

References 132 publications

Nucleotide specificity of the human terminal nucleotidyltransferase Gld2 (TUT2)

Nucleotide specificity of the human terminal nucleotidyltransferase Gld2 (TUT2)

Diagnostic utility of miRNAs in cancer A review

Cancer stem cells as a potential therapeutic target in thyroid carcinoma

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