MicroRNA in carcinogenesis & cancer diagnostics: a new paradigm (original) (raw)
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MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.
MicroRNA expression and function in cancer
Trends in Molecular Medicine, 2006
MicroRNAs are small non-coding RNAs of 19-24 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Recent work supports a role for miRNAs in the initiation and progression of human malignancies. Large high-throughput studies in patients revealed that miRNA profiling have the potential to classify tumors with high accuracy and predict outcome. Functional studies, some of which involve animal models, indicate that miRNAs act as tumor suppressors and oncogenes. Here, we summarize miRNA-profiling studies in human malignancies and examine the role of miRNAs in the pathogenesis of cancer. We also discuss the implications of these findings for the diagnosis and treatment of cancer.
MicroRNA and cancer: Current status and prospective
International Journal of Cancer, 2006
Gene expression in normal cells is highly regulated by complex gene regulatory networks. Disruption of these networks may lead to cancer. Recent studies have revealed the existence of an abundant class of small nonprotein-coding regulatory RNAs, known as microRNAs (miRNAs). MiRNAs may regulate diverse biological processes including development, cell proliferation, differentiation and apoptosis, through suppressing the expression of their target genes. Posttranscriptional silencing of target genes by miRNAs occurs either by cleavage of homologous target messenger RNAs (mRNAs), or by inhibition of target protein synthesis. Computational predictions indicate that 1 miRNA may target on hundreds of genes, and suggest that over 50% of human protein-coding genes might be regulated by miRNAs. MiRNAs are receiving increased attention in cancer genomic research. We are beginning to understand that miRNAs may act as oncogenes and/or tumor suppressor genes within the molecular architecture of gene regulatory networks, thereby contributing to the development of cancer. MiRNAs may provide useful diagnostic and prognostic markers for cancer diagnosis and treatment, as well as serving as potential therapeutic targets or tools.
MicroRNAs and cancer: An overview
Cell Cycle, 2008
MicroRNAs (miRNAs) are a recently discovered class of small RNA molecules that negatively regulate gene expression at the posttranscriptional level. MiRNAs play key roles in development and establishment of cell identity and aberrant metabolism/expression of miRNAs has been linked to human diseases including cancer. Components of the miRNA machinery and miRNAs themselves are involved in many cellular processes that are altered in cancer, such as differentiation, proliferation and apoptosis. Some miRNAs exhibit differential expression levels in cancer and have demonstrated capability to affect cellular transformation, carcinogenesis and metastasis acting either as oncogenes or tumour suppressors. We are only beginning to comprehend the functional repercussions of the gain or loss of particular microRNAs on cancer. Nonetheless, although microRNAs have been discovered in humans a mere eight years ago, a host of promising potential applications in the diagnosis, prognoses and therapy of cancer are emerging at a rapid pace.
MicroRNAs: Key players in carcinogenesis and novel therapeutic targets
European Journal of Surgical Oncology (EJSO), 2009
MicroRNAs (miRNAs) represent a recently uncovered class of small and endogenous non-coding RNAs. MiRNA function is critical to normal cellular processes such as differentiation and apoptosis, and recent studies have demonstrated that deregulated miRNA expression contributes to the malignant phenotype. The purpose of this review is to summarise these findings in relation to the most common human malignancies, and to analyse the clinical and therapeutic opportunities they provide.
ANNUAL REVIEW OF MEDICINEBook Series Annual Review of Medicine, 2009
During the last few years, studies on microRNA (miRNA) and cancer have burst onto the scene. Profiling of the miRNome (global miRNA expression levels) has become prevalent and abundant miRNome data are currently available from various cancers. The pattern of miRNA expression can be correlated with cancer type, stage, and other clinical variables, so that miRNA profiling can be used as a tool for cancer diagnosis and prognosis. miRNA expression analyses also suggested oncogenic (or tumor suppressive) roles of miRNAs. miRNAs play roles in almost all aspects of cancer biology such as proliferation, apoptosis, invasion/metastasis, and angiogenesis. Given that many miRNAs are deregulated in cancers but have not yet been further studied, it is expected that more miRNAs will emerge as players in the etiology and progression of cancer. miRNAs will be also discussed as a tool for cancer therapy. SYNOPSIS-During the last decade, a major discovery in biology was the discovery of small RNAs, including miRNA (microRNA) and siRNA (small interfering RNA), as highlighted by the 2002 December issue of Science magazine (1). Since RNA interference (RNAi) phenomenon was discovered in nematodes (2), siRNA has provided a technical breakthrough for short term genetics in mammalian systems. The big impact of small RNAs was well celebrated by the 2006 Nobel prize awarded to the two scientists who discovered RNAi. On the other side, miRNAs shed new insight on the post-transcriptional regulation of gene expression. miRNAs were also first discovered in worms (3,4), and later in a number of animals, plants, and viruses. During the last couple of years, the miRNA field has been expanding with many recent publications implicating miRNAs in diverse cellular processes. Cancer is a major cause of death in the United States ("Cancer Facts & Figures 2007" from American Cancer Society; http://www.cancer.org/docroot/stt/stt\_0.asp). Cancer is a complex genetic disease caused by the accumulation of mutations that lead to deregulation of gene expression and uncontrolled cell proliferation. Given the wide impact of miRNAs on gene expression, it is not surprising that a number of miRNAs have been implicated in cancer. In this review, the links between miRNA and cancer will be comprehensively described and discussed.
MicroRNAs: Potential biomarkers in cancer
Indian Journal of Clinical Biochemistry, 2010
microRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs, also known as micromanagers of gene expression. Polymorphisms in the miRNA pathway (miR-polymorphisms) are emerging as powerful tools to study the biology of a disease and have the potential to be used in disease prognosis and diagnosis. Advancements in the miRNA field also indicate a clear involvement of deregulated miRNA gene signatures in cancers, and several polymorphisms in pre-miRNA, miRNA binding sites or targets have been found to be associated with various cancers. The miRNA polymorphisms have also been reported to influence tumor aggressiveness as well as survival of cancer patients. miRNAs have a revolutionary impact on cancer research over recent years. They emerge as important players in tumorigenesis, leading to a paradigm shift in oncology. The extensive and comprehensive use of miRNA microarrays has enabled the identification of a number of miRNAs as potential biomarkers for cancer. Many miRNAs have been identified to act as oncogenes, tumor suppressors, or even modulators of cancer stem cells and metastasis. Some studies not only reported the identified miRNA biomarkers, but also deciphered their target genes and the underlying mechanisms. The rapid discovery of many miRNA targets and their relevant pathways has contributed to the development of miRNA-based therapeutics.
microRNAs as oncogenes and tumor suppressors
Developmental Biology, 2007
microRNAs (miRNAs) are a new class of non-protein-coding, endogenous, small RNAs. They are important regulatory molecules in animals and plants. miRNA regulates gene expression by translational repression, mRNA cleavage, and mRNA decay initiated by miRNA-guided rapid deadenylation. Recent studies show that some miRNAs regulate cell proliferation and apoptosis processes that are important in cancer formation. By using multiple molecular techniques, which include Northern blot analysis, real-time PCR, miRNA microarray, up-or down-expression of specific miRNAs, it was found that several miRNAs were directly involved in human cancers, including lung, breast, brain, liver, colon cancer, and leukemia. In addition, some miRNAs may function as oncogenes or tumor suppressors. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites, suggesting that miRNAs may play a more important role in the pathogenesis of a limited range of human cancers than previously thought. Overexpressed miRNAs in cancers, such as mir-17-92, may function as oncogenes and promote cancer development by negatively regulating tumor suppressor genes and/or genes that control cell differentiation or apoptosis. Underexpressed miRNAs in cancers, such as let-7, function as tumor suppressor genes and may inhibit cancers by regulating oncogenes and/or genes that control cell differentiation or apoptosis. miRNA expression profiles may become useful biomarkers for cancer diagnostics. In addition, miRNA therapy could be a powerful tool for cancer prevention and therapeutics.
MicroRNAs: molecular features and role in cancer
Frontiers in Bioscience
microRNAs (miRNAs) are small noncoding endogenously produced RNAs that play key roles in controlling the expression of many cellular proteins. Once they are recruited and incorporated into a ribonucleoprotein complex miRISC, they can target specific mRNAs in a miRNA sequence-dependent process and interfere in the translation into proteins of the targeted mRNAs via several mechanisms. Consequently, miRNAs can regulate many cellular pathways and processes. Dysregulation of their physiological roles may largely contribute to disease. In particular, in cancer, miRNAs can be involved in the deregulation of the expression of important genes that play key roles in tumorigenesis, tumor development, and angiogenesis and have oncogenic or tumor suppressor roles. This review focuses on the biogenesis and maturation of miRNAs, their mechanisms of gene regulation, and the way their expression is deregulated in cancer. The involvement of miRNAs in several oncogenic pathways such as angiogenesis a...
MicroRNA: A signature for cancer progression
MicroRNAs (miRNAs) are a group of small non-coding RNAs that post-transcriptionally control expression of genes by targeting mRNAs. miRNA alterations partake in the establishment and progression of different types of human cancer. Consequently, expression profiling of miRNA in human cancers has correlations with cancer detection, staging, progression, and response to therapies. Particularly, amplification, deletion, abnormal pattern of epigenetic factors and the transcriptional factors that mediate regulation of primary miRNA frequently change the landscape of miRNA expression in cancer. Indeed, changes in the quantity and quality of miRNAs are associated with the initiation of cancer, its progression and metastasis. Additionally, miRNA profiling has been used to categorize genes that can affect oncogenic pathways in cancer. Here, we discuss several circulating miRNA signatures, their expression profiles in different types of cancer and their impacts on cellular processes.