Molecular Pathways: MicroRNAs as Cancer Therapeutics (original) (raw)
Related papers
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.
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 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.
MicroRNAs in cancer — from research to therapy
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2010
MicroRNAs (miRNAs) regulate target gene expression through translation repression or mRNA degradation. These non-coding RNAs are emerging as important modulators in cellular pathways, and they appear to play a key role in tumorigenesis. With increasing understanding of the miRNA target genes and the cellular behaviors influenced by them, modulating the miRNA activities may provide exciting opportunities for cancer therapy. Here the latest findings of which genes are targeted by each miRNA are reviewed, with particular emphasis on the deciphering of their possible mechanisms and the potential of miRNA-based cancer therapeutics.
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.
Journal of Internal Medicine, 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 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.
miRNAs as targets for cancer treatment: Therapeutics design and delivery
Advanced Drug Delivery Reviews, 2015
MicroRNAs (miRNAs) are a class of post-transcriptional gene expression modulators. In the past two decades, over 1500 human miRNAs were discovered. Each miRNA controls hundreds of gene targets through imperfect complimentary miRNA-mRNA binding. These small non-coding RNAs regulate various biological processes, including cell growth, proliferation, differentiation, and cell death. ☆ This preface is part of the Advanced Drug Delivery Reviews theme issue on "miRNAs as targets for cancer treatment: Therapeutics design and delivery".
Therapeutic implications of microRNAs in human cancer
MicroRNAs (miRNAs) are a class of highly evolutionarily conserved non-coding RNAs (ncRNAs) that modulate gene expression. Several studies have shown that the expression of miRNAs is deregulated in human malignancies. For ncRNAs and miRNAs, such gene-profiling studies in tumorigenic tissues have identified significant signatures that are of both diagnostic and prognostic value. Addressing the functions of ncRNAs not only give insights into the molecular mechanisms that underlie complex genetic processes, but may also elucidate novel mechanisms that contribute to early stages of tumor development, progression and metastasis. MiRNA-based novel approaches target the ncRNAome, including, for instance, miRNA expression levels and improved designs of miRNA-mimics or more precise target-predictions, prevent offtarget effects of novel drugs and make miRNAs become a highly efficient class of therapeutics. For miRNA-based therapeutic studies two direct strategies are currently under investigation, viz. (i) the overexpression of given miRNAs to inhibit the expression of proteincoding genes or (ii) the inhibition of target miRNAs with antisense constructs like antagomiRs. Indirect strategies include the use of novel drugs that modulate miRNA expression levels by directly targeting their processing or transcription. Further, miRNAbased biomarkers have a significant impact on the development of both therapeutic and diagnostic agents, a concept known as theranostics and are highly relevant for drug development and personalized medicine.