As a type of short noncoding RNAs, microRNA (miRNA) undoubtedly plays a crucial role in cancer development. Since the discovery of the identity and clinical functions of miRNAs, over the past few ...decades, the roles of miRNAs in cancer have been actively investigated. Numerous pieces of evidence indicate that miRNAs are pivotal factors in most types of cancer. Recent cancer research focused on miRNAs has identified and characterized a large cohort of miRNAs commonly dysregulated in cancer or exclusively dysregulated in specific types of cancer. These studies have suggested the potential of miRNAs as biomarkers in the diagnosis and prognostication of cancer. Moreover, many of these miRNAs have oncogenic or tumor-suppressive functions. MiRNAs have been the focus of research given their potential clinical applications as therapeutic targets. Currently, various oncology clinical trials using miRNAs in screening, diagnosis, and drug testing are underway. Although clinical trials studying miRNAs in various diseases have been reviewed before, there have been fewer clinical trials related to miRNAs in cancer. Furthermore, updated results of recent preclinical studies and clinical trials of miRNA biomarkers and drugs in cancer are needed. Therefore, this review aims to provide up-to-date information on miRNAs as biomarkers and cancer drugs in clinical trials.
MicroRNAs in cancer Di Leva, Gianpiero; Garofalo, Michela; Croce, Carlo M
Annual review of pathology,
01/2014, Letnik:
9
Journal Article
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MicroRNAs (miRNAs) are small noncoding RNAs that typically inhibit the translation and stability of messenger RNAs (mRNAs), controlling genes involved in cellular processes such as inflammation, ...cell-cycle regulation, stress response, differentiation, apoptosis, and migration. Thus, miRNAs have been implicated in the regulation of virtually all signaling circuits within a cell, and their dysregulation has been shown to play an essential role in the development and progression of cancer. Here, after a brief description of miRNA genomics, biogenesis, and function, we discuss the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies.
The role of MicroRNAs in human cancer Peng, Yong; Croce, Carlo M
Signal transduction and targeted therapy,
01/2016, Letnik:
1, Številka:
1
Journal Article
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MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that function in regulation of gene expression. Compelling evidences have demonstrated that miRNA expression is dysregulated in human cancer ...through various mechanisms, including amplification or deletion of miRNA genes, abnormal transcriptional control of miRNAs, dysregulated epigenetic changes and defects in the miRNA biogenesis machinery. MiRNAs may function as either oncogenes or tumor suppressors under certain conditions. The dysregulated miRNAs have been shown to affect the hallmarks of cancer, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, activating invasion and metastasis, and inducing angiogenesis. An increasing number of studies have identified miRNAs as potential biomarkers for human cancer diagnosis, prognosis and therapeutic targets or tools, which needs further investigation and validation. In this review, we focus on how miRNAs regulate the development of human tumors by acting as tumor suppressors or oncogenes.
Over the past several years it has become clear that alterations in the expression of microRNA (miRNA) genes contribute to the pathogenesis of most--if not all--human malignancies. These alterations ...can be caused by various mechanisms, including deletions, amplifications or mutations involving miRNA loci, epigenetic silencing or the dysregulation of transcription factors that target specific miRNAs. Because malignant cells show dependence on the dysregulated expression of miRNA genes, which in turn control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumour suppressor genes, these small RNAs provide important opportunities for the development of future miRNA-based therapies.
In 1984, we investigated the t(14;18) chromosomal translocations that frequently occur in patients with follicular lymphoma. We first identified a locus on chromosome 18 involved in these ...translocations with the chromosome 14 containing the immunoglobulin heavy chain locus. Within this region on chromosome 18, we then discovered a gene that we called BCL2, which was activated by the translocations. Since that time, many studies determined that BCL2 is one of the most important oncogenes involved in cancer by inhibiting apoptosis. In 2002, we studied 13q deletions in chronic lymphocytic leukemia (CLL) and found that the microRNA cluster miR-15a/miR-16-1 (miR-15/16) is deleted by 13q deletions. In 2005, we discovered that miR-15/16 function as tumor suppressors by directly targeting BCL2. Thus the loss of two negative regulators of BCL2 expression results in overexpression of BCL2. Very recently, a specific BCL2 inhibitor ABT-199 (Venetoclax) was developed and approved by FDA for CLL treatment. Thus it took 32 years from fundamental discovery of a critical oncogene to the development of a drug capable to cure CLL. In this review, we discuss the discovery, functions and clinical relevance of miR-15/16 and BCL2.
miRNA profiling of cancer Di Leva, Gianpiero; Croce, Carlo M
Current opinion in genetics & development,
02/2013, Letnik:
23, Številka:
1
Journal Article
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A steadily growing number of studies have shown that microRNAs have key roles in the regulation of cellular processes and that their dysregulation is essential to keep the malignant phenotype of ...cancer cells. The distorted and unique expression profile of microRNAs in different types and subsets of tumor coupled with their presence in biological fluids make of microRNAs an attractive source of sensitive biomarkers. Here, we will discuss how microRNA profiles are altered in cancer, highlighting their potential as sensitive biomarkers for cancer risk stratification, outcome prediction and classification of histological subtypes. We will also evaluate the current knowledge on the use of microRNAs as circulating biomarkers, hoping that further studies will lead to the application of microRNA signature in prognostic and predictive markers that can improve patient health.
Early studies have shown how aberrantly expressed microRNAs are a hallmark of several diseases like cancer. MicroRNA expression profiling was shown to be associated with tumour development, ...progression and response to therapy, suggesting their possible use as diagnostic, prognostic and predictive biomarkers. Moreover, based on the increasing number of studies demonstrating that microRNAs can function as potential oncogenes or oncosuppressor genes, with the goal to improve disease response and increase cure rates, miRNA‐based anticancer therapies have recently been exploited, either alone or in combination with current targeted therapies. The advantage of using microRNA approaches is based on its ability to concurrently target multiple effectors of pathways involved in cell differentiation, proliferation and survival. Here, we review our current knowledge about the involvement of microRNAs in cancer, and their potential as diagnostic, prognostic and therapeutic tools.
Small non-coding RNA and cancer Romano, Giulia; Veneziano, Dario; Acunzo, Mario ...
Carcinogenesis (New York),
05/2017, Letnik:
38, Številka:
5
Journal Article
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The ENCODE project has reported that at least 80% of the human genome is biologically active, yet only a small part of human DNA encodes for protein. The massive amount of RNA transcribed but not ...translated into protein can be classified as housekeeping RNA (such as rRNA, tRNA) and regulatory RNA (such as miRNA, piRNA, lncRNA). Small non-coding RNAs, in particular, have been the focus of many studies in the last 20 years and their fundamental role in many human diseases is currently well established. Inter alia, their role in cancer development and progression, as well as in drug resistance, is being increasingly investigated. In this review, focusing our attention on recent research results, we provide an overview of the four large classes of small non-coding RNAs, namely, miRNAs, piRNAs, snoRNA and the new class of tRNA-derived fragments, highlighting their fundamental role in cancer and their potential as diagnostic and prognostic biomarkers.
Every cellular process is likely to be regulated by microRNAs, and an aberrant microRNA expression signature is a hallmark of several diseases, including cancer. MicroRNA expression profiling has ...indeed provided evidence of the association of these tiny molecules with tumor development and progression. An increasing number of studies have then demonstrated that microRNAs can function as potential oncogenes or oncosuppressor genes, depending on the cellular context and on the target genes they regulate. Here we review our current knowledge about the involvement of microRNAs in cancer and their potential as diagnostic, prognostic, and therapeutic tools.
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