MicroRNAs in cancer — from research to therapy (original) (raw)
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MicroRNAs as Molecular Targets for Cancer Therapy: On the Modulation of MicroRNA Expression
Pharmaceuticals, 2013
The discovery of small RNA molecules with the capacity to regulate messenger RNA (mRNA) stability and translation (and consequently protein synthesis) has revealed an additional level of post-transcriptional gene control. MicroRNAs (miRNAs), an evolutionarily conserved class of small noncoding RNAs that regulate gene expression post-transcriptionally by base pairing to complementary sequences in the 3' untranslated regions of target mRNAs, are part of this modulatory RNA network playing a pivotal role in cell fate. Functional studies indicate that miRNAs are involved in the regulation of almost every biological pathway, while changes in miRNA expression are associated with several human pathologies, including cancer. By targeting oncogenes and tumor suppressors, miRNAs have the ability to modulate key cellular processes that define the cell phenotype, making them highly promising therapeutic targets. Over the last few years, miRNA-based anti-cancer therapeutic approaches have been exploited, either alone or in combination with standard targeted therapies, aiming at enhancing tumor cell killing and, ideally, promoting tumor regression and disease remission. Here we provide an overview on the involvement of miRNAs in cancer pathology, emphasizing the mechanisms of miRNA regulation. Strategies for modulating miRNA expression are presented and illustrated with representative examples of their application in a therapeutic context.
Recent trends in targeting miRNAs for cancer therapy
Journal of Pharmacy and Pharmacology, 2020
Objectives MicroRNAs (miRNAs) are a type of small noncoding RNA employed by the cells for gene regulation. A single miRNA, typically 22 nucleotides in length, can regulate the expression of numerous genes. Over the past decade, the study of miRNA biology in the context of cancer has led to the development of new diagnostic and therapeutic opportunities. Key findings MicroRNA dysregulation is commonly associated with cancer, in part because miRNAs are actively involved in the mechanisms like genomic instabilities, aberrant transcriptional control, altered epigenetic regulation and biogenesis machinery defects. MicroRNAs can regulate oncogenes or tumour suppressor genes and thus when altered can lead to tumorigenesis. Expression profiling of miRNAs has boosted the possibilities of application of miRNAs as potential cancer biomarkers and therapeutic targets, although the feasibility of these approaches will require further validation. Summary In this review, we will focus on how miRNAs...
MicroRNAs as Cancer Players: Potential Clinical and Biological Effects
DNA and Cell Biology, 2007
MicroRNAs (miRNAs) are nonprotein-coding RNAs that function as posttranscriptional gene regulators. They can regulate their targets directly by mRNA cleavage or by repressing their translation, depending on the degree of complementariety between the miRNA and the target. Recent evidences have shown that miRNA control cell growth, apoptosis, and differentiation. Moreover, miRNA expression correlates with cancers and could have a crucial function in tumor progression. Bioinformatic data indicates that each miRNA can control hundreds of target genes, but identification of the accurate miRNA targets will be crucial to exploit the emerging knowledge of miRNA contribution to cancer process. While the miRNA field is still emerging, the benefit of our understanding of miRNA in cancer is potentially enormous, especially if we are able to apply this knowledge to provide new therapies for patients.
MicroRNAs and Cancer Therapy – From Bystanders to Major Players
MicroRNAs (miRNAs) are an evolutionarily conserved class of small regulatory RNAs that modulate gene expression. Extensive research over the last decade has shown that miRNAs are master regulators of cellular processes, with an essential role in cancer initiation, progression, and metastasis. Widespread deregulation of miRNAs in cancers has identified oncogenic and tumor-suppressive roles for these miRNAs. On the basis of these observations, miRNAs have emerged as promising therapeutic tools for cancer management. In this review, we focus on the roles of miRNAs in tumorigenesis, the rationale and strategies for the use of miRNA-based therapy for cancer, and the advantages and current challenges to their use.
microRNAs: New-Age Panacea in Cancer Therapeutics
Indian Journal of Surgical Oncology, 2020
MicroRNAs (miRNAs) are small (~18-25 nucleotides in length), endogenous, non-coding RNAs, which regulate gene expression. Numerous studies have demonstrated the dysregulation of miRNA expression in human cancers through various mechanisms, which include genetic alteration of miRNA genes, abnormal transcriptional control of miRNAs, anomalous epigenetic changes, and defective miRNA biogenesis machinery. They may function as either oncomiRs or tumor suppressor miRNAs in a tissue or cell-specific manner. The dysregulated miRNAs are known to affect the hallmarks of cancer, and some of these miRNAs have shown therapeutic promise in pre-clinical and clinical studies. Here, we briefly touch upon various aspects of miRNA biology with a particular focus on their roles in cancer.
Molecular and Cellular Therapies, 2014
MicroRNAs (miRNAs or miRs) are a family of small non-coding RNA species that have been implicated in the control of many fundamental cellular and physiological processes such as cellular differentiation, proliferation, apoptosis and stem cell maintenance. miRNAs regulate gene expression by the sequence-selective targeting of mRNAs, leading to translational repression or mRNA degradation. Some microRNAs have been categorized as "oncomiRs" as opposed to "tumor suppressor miRs" Modulating the miRNA activities may provide exciting opportunities for cancer therapy. This review highlights the latest discovery of miRNAs involved in carcinogenesis as well as the potential applications of miRNA regulations in cancer treatment. Several studies have demonstrated the feasibility of restoring tumor suppressive miRNAs and targeting oncogenic miRNAs for cancer therapy using in vivo model systems.
Molecular Pathways: MicroRNAs as Cancer Therapeutics
Clinical Cancer Research, 2012
MicroRNAs (miRNA) are approximately 18 to 25 nucleotides in length and affect gene expression by silencing the translation of messenger RNAs. Because each miRNA regulates the expression of hundreds of different genes, miRNAs can function as master coordinators, efficiently regulating and coordinating multiple cellular pathways and processes. By coordinating the expression of multiple genes, miRNAs are responsible for fine-tuning the cell's most important processes, like the ones involved in cellular growth and proliferation. Dysregulation of miRNAs appears to play a fundamental role in the onset, progression and dissemination of many cancers, and replacement of downregulated miRNAs in tumor cells results in a positive therapeutic response. Thus, in theory, inhibition of a particular miRNA linked to cancer onset or progression can remove the inhibition of the translation of a therapeutic protein—and conversely, administration of a miRNA mimetic can boost the endogenous miRNA popu...
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...
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 (miRNAs) are a class of highly evolutionarily conserved non-coding RNAs (ncRNAs) that modulate gene expression. They play fundamental roles in the regulation of gene expression by pairing via partial Watson and Crick interactions with complementary sequences within the 3¢ untranslated regions (3¢UTRs) of targeted transcripts [1] and several studies have shown that the expression of miRNAs is deregulated in human malignancies. For ncRNAs and miRNAs, such geneprofiling studies in tumorigenic tissues have identified significant signatures that are of both diagnostic and prognostic value. The challenge is to translate the numerous known examples linking dysregulated expression of miRNAs to cancer into the development of novel therapeutics.