Everything you wanted to know about small RNA but were afraid to ask

Boyd, Scott D.

doi:10.1038/labinvest.2008.32

Cited by 89 publications

(81 citation statements)

References 151 publications

(168 reference statements)

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“…RNA-inducing silencing complex and miRs regulate the amount of protein expressed from coding RNAs by translational repression or by cleavage of the target mRNA due to base pairing with the 3′ untranslated region (UTR). MiRs have been linked to essential physiologic processes such as regulation of proliferation, differentiation, and apoptosis (1)(2)(3)(4) and to several diseases including cancer (5,6).…”

Section: Introductionmentioning

confidence: 99%

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Hofmann

Heinrich

Radziwil

et al. 2009

Molecular Cancer Research

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The noncoding RNA miR-125b has been described to reduce ErbB2 protein expression as well as proliferation and migration of cancer cell lines. As additional target of miR-125b, we identified the c-raf-1 mRNA by sequence analysis. We designed a short hairpin-looped oligodeoxynucleotide (ODN) targeted to the same 3′ untranslated region of c-raf-1 mRNA as miR-125b. The fully complementary ODN antisense strand is linked to a second strand constituting a partially double-stranded structure of the ODN. Transfection of the c-raf-1-specific ODN (ODN-Raf) in a breast cancer cell line reduced the protein levels of C-Raf, ErbB2, and their downstream effector cyclin D1 similar to miR-125b. MiR-125b as well as ODN-Raf showed no effect on the c-raf-1 mRNA level in contrast to small interfering RNA. Unlike miR-125b, ODN-Raf induced a cytopathic effect. This may be explained by the structural properties of ODN-Raf, which can form G-tetrads. Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death. Both features may be useful to interfere with tumor growth. (Mol Cancer Res 2009;7(10):1635-44)

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Section: Introductionmentioning

confidence: 99%

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Hofmann

Heinrich

Radziwil

et al. 2009

Molecular Cancer Research

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“…MicroRNA (miR) are small single-stranded non-coding RNA molecules of about 21-23 nucleotides in length, which regulate gene expression by targeting mRNA for degradation or translational repression at the post-transcriptional level. Studies in human cells have only begun to reveal the mechanisms of miR regulation activity, the normal physiological functions they influence and how their alteration can lead to pathologies [18]. miR recognize their targets by base pairing with a short region of about seven nucleotides, either in the translated region, or in the 3 0 untranslated region (3 0 UTR) of their target mature mRNA.…”

Section: Cd25mentioning

confidence: 99%

Human natural Treg microRNA signature: Role of microRNA‐31 and microRNA‐21 in FOXP3 expression

et al. 2009

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Treg are the main mediators of dominant tolerance. Their mechanisms of action and applications are subjects of considerable debate currently. However, a human microRNA (miR) Treg signature has not been described yet. We investigated human natural Treg and identified a signature composed of five miR (21, 31, 125a, 181c and 374). Among those, two were considerably under-expressed (miR-31 and miR-125a). We identified a functional target sequence for miR-31 in the 3 0 untranslated region (3 0 UTR) of FOXP3 mRNA. Using lentiviral transduction of fresh cord blood T cells, we demonstrated that miR-31 and miR-21 had an effect on FOXP3 expression levels. We showed that miR-31 negatively regulates FOXP3 expression by binding directly to its potential target site in the 3 0 UTR of FOXP3 mRNA. We next demonstrated that miR-21 acted as a positive, though indirect, regulator of FOXP3 expression. Transduction of the remaining three miR had no direct effect on FOXP3 expression or on the phenotype and will remain the subject of future investigations. In conclusion, not only have we identified and validated a miR signature for human natural Treg, but also unveiled some of the mechanisms by which this signature was related to the control of FOXP3 expression in these cells.

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“…160 These microRNAs have important and diversified functions including cell differentiation, 161 tumorigenesis 162 and viral defense. 163 As a result, the possibility that class II gene expression could be regulated by microRNAs, and more specifically, differentially regulated based on underlying sequence variation, needs to be examined.…”

Section: Mhc Class II Expression Polymorphism and Disease L Handunnementioning

confidence: 99%

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

et al. 2009

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Major histocompatibility complex (MHC) class II molecules are central to adaptive immune responses and maintenance of selftolerance. Since the early 1970s, the MHC class II region at chromosome 6p21 has been shown to be associated with a remarkable number of autoimmune, inflammatory and infectious diseases. Given that a full explanation for most MHC class II disease associations has not been reached through analysis of structural variation alone, in this review we examine the role of genetic variation in modulating gene expression. We describe the intricate architecture of the MHC class II regulatory system, indicating how its unique characteristics may relate to observed associations with disease. There is evidence that haplotypespecific variation involving proximal promoter sequences can alter the level of gene expression, potentially modifying the emergence and expression of key phenotypic traits. Although much emphasis has been placed on cis-regulatory elements, we also examine the role of more distant enhancer elements together with the evidence of dynamic inter-and intra-chromosomal interactions and epigenetic processes. The role of genetic variation in such mechanisms may hold profound implications for susceptibility to common disease.

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Everything you wanted to know about small RNA but were afraid to ask

Cited by 89 publications

References 151 publications

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Human natural Treg microRNA signature: Role of microRNA‐31 and microRNA‐21 in FOXP3 expression

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

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