SNPs in MicroRNA Binding Sites as Prognostic and Predictive Cancer Biomarkers

Preskill, Carina; Weidhaas, Joanne B.

doi:10.1615/critrevoncog.2013007254

Cited by 38 publications

(27 citation statements)

References 64 publications

(73 reference statements)

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“…On a separate note, single nucleotide polymorphisms (SNP, see Table 1 for definition) in the protein‐coding mRNAs targeted by miRNAs have shown to influence cancer risk as well. For example, let‐7, a tumor suppressor miRNA known to target the mRNA of the KRAS oncogene, has been proven to be unable to bind to a KRAS SNP variant found to be disproportionately enriched in non‐small cell lung carcinoma (NSCLC) (present in 18%‐20% of cases) . This same KRAS variant was also associated with an increased risk of developing epithelial ovarian cancer, a finding that was consistent among 3 independent cohorts and 2 case‐control studies .…”

Section: Mirnas As Ubiquitous Players In Cancermentioning

confidence: 85%

MicroRNAome genome: A treasure for cancer diagnosis and therapy

Berindan‐Neagoe

Monroig

Pasculli

et al. 2014

CA A Cancer J Clinicians

439

381

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The interplay between abnormalities in genes coding for proteins and microRNAs (miRNAs) has been among the most exiting yet unexpected discoveries in oncology over the last decade. The complexity of this network has redefined cancer research as these molecules produced from what was once considered “genomic trash”, have shown to be crucial for cancer initiation, progression, and dissemination. Naturally occurring miRNAs are very short transcripts that never produce a protein or amino acid chain, but act by regulating protein expression during cellular processes such as growth, development and differentiation at the transcriptional, post-transcriptional and/or translational level. In this review article we present miRNAs as ubiquitous players involved in all cancer hallmarks. We also describe the most used methods to detect their expression, which have revealed through gene expression studies the identity of hundreds of miRNAs dysregulated in cancer cells or tumor microenvironment cells. Furthermore, we discuss the role of miRNAs as hormones and as reliable cancer biomarkers and predictors of treatment-response. Along with this, we explore current strategies in designing miRNA-targeting therapeutics, as well as the associated challenges that research envisions to overcome. Finally, we introduce a new wave in molecular oncology translational research, the study of long non-coding RNAs.

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Section: Mirnas As Ubiquitous Players In Cancermentioning

confidence: 85%

MicroRNAome genome: A treasure for cancer diagnosis and therapy

Berindan‐Neagoe

Monroig

Pasculli

et al. 2014

CA A Cancer J Clinicians

439

381

View full text Add to dashboard Cite

show abstract

“…However, some functional polymorphysms in miRNA genes have been discovered that might be relevant in the progression of diseases such as acute lymphoblastic leukemia 30 and diabetic retinopathy. 31 Over the past few years, several examples of these functional miRNA binding site single nucleotide polymorphisms have been identified as biomarkers for different pathologies including cancer 32 and rheumatoid arthritis. 33 An additional area of interest in miRNA research is the use of circulating miRNAs as biomarkers of human diseases.…”

Section: Introductionmentioning

confidence: 99%

Role of MicroRNAs in the Trabecular Meshwork

González

Qiu

et al. 2014

Journal of Ocular Pharmacology and Therapeutics

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MicroRNAs (miRNAs) are now recognized as important post-transcriptional regulators of gene expression. MiRNAs are known to modulate cellular functions relevant to the normal and pathological physiology of the trabecular meshwork (TM) such as cell contraction and extracellular matrix turnover. There is also increasing evidence supporting the role of miRNAs in the pathogenesis of multiple diseases, and their potential value as both biomarkers of disease and therapeutic targets. However, compared with other tissues, our current knowledge regarding the roles played by miRNAs in the TM is still very limited. Here, we review the information currently available about miRNAs in the TM and discuss the main challenges and opportunities to incorporate the rapid progress in miRNA biology to the understanding of the normal and pathological physiology of the TM, and to develop novel clinical applications for diagnosis and therapy of high intraocular pressure.

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“…Increasing evidence suggests that dysregulated miRNAs directly contribute to the pathogenesis of a variety of human diseases [30][31][32][33][34]. SNPs in miRNA target sites in the 3' UTR of mRNAs are referred to as polymorphisms in microRNAs and their target sites (polymiRTSs) and can affect mRNA half-life, resulting in decreased protein levels due to mRNAmiRNA interactions and increased susceptibility to many diseases [30-33, 35, 36], including PD [33].…”

Section: Discussionmentioning

confidence: 99%

miR-486-3p Influences the Neurotoxicity of a-Synuclein by Targeting the SIRT2 Gene and the Polymorphisms at Target Sites Contributing to Parkinson’s Disease

Wang

Cai

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Increasing evidence suggests the important role of sirtuin 2 (SIRT2) in the pathology of Parkinson’s disease (PD). However, the association between potential functional polymorphisms in the SIRT2 gene and PD still needs to be identified. Exploring the molecular mechanism underlying this potential association could also provide novel insights into the pathogenesis of this disorder. Methods: Bioinformatics analysis and screening were first performed to find potential microRNAs (miRNAs) that could target the SIRT2 gene, and molecular biology experiments were carried out to further identify the regulation between miRNA and SIRT2 and characterize the pivotal role of miRNA in PD models. Moreover, a clinical case-control study was performed with 304 PD patients and 312 healthy controls from the Chinese Han population to identify the possible association of single nucleotide polymorphisms (SNPs) within the miRNA binding sites of SIRT2 with the risk of PD. Results: Here, we demonstrate that miR-486-3p binds to the 3’ UTR of SIRT2 and influences the translation of SIRT2. MiR-486-3p mimics can decrease the level of SIRT2 and reduce a-synuclein (α-syn)-induced aggregation and toxicity, which may contribute to the progression of PD. Interestingly, we find that a SNP, rs2241703, may disrupt miR-486-3p binding sites in the 3’ UTR of SIRT2, subsequently influencing the translation of SIRT2. Through the clinical case-control study, we further verify that rs2241703 is associated with PD risk in the Chinese Han population. Conclusion: The present study confirms that the rs2241703 polymorphism in the SIRT2 gene is associated with PD in the Chinese Han population, provides the potential mechanism of the susceptibility locus in determining PD risk and reveals a potential target of miRNA for the treatment and prevention of PD.

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SNPs in MicroRNA Binding Sites as Prognostic and Predictive Cancer Biomarkers

Cited by 38 publications

References 64 publications

MicroRNAome genome: A treasure for cancer diagnosis and therapy

MicroRNAome genome: A treasure for cancer diagnosis and therapy

Role of MicroRNAs in the Trabecular Meshwork

miR-486-3p Influences the Neurotoxicity of a-Synuclein by Targeting the SIRT2 Gene and the Polymorphisms at Target Sites Contributing to Parkinson’s Disease

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