RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs

Bajan, Sarah; Hutvágner, György

doi:10.3390/cells9010137

Cited by 282 publications

(233 citation statements)

References 204 publications

(214 reference statements)

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“…Our study has indicated the melanoma cells are highly vulnerable to the decrease in K1, suggesting that K1 may be a novel valuable target for treating melanoma cells. RNAi approach has become a promising technology for treating multiple diseases [1]. It is expected that RNAi approach is capable of producing at least a mild decrease in the K1 levels of melanoma cells, which may produce therapeutic effects on melanomas.…”

Section: Discussionmentioning

confidence: 99%

A Mild Keratin 1 Decrease Leads to Cell Death and Increased Oxidative Stress in B16-F10 Melanoma Cell Lines

Zhang

Ying

2020

Preprint

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Keratins play multiple significant biological roles in epithelium. K1 / keratin 10 (K10) heterodimer is a hallmarker for keratinocyte differentiation. While keratins are absent in normal melanocyte, keratins have been found in both melanoma cell lines and human melanoma. The biological significance of the keratins in melanoma cells has remained unclear. In our current study we applied K1 siRNA to investigate the biological significance of the K1 in B16-F10 melanoma cells. We found that as low as a 16% decrease in the K1 level led to significant increases in both apoptosis and necrosis of the cells. Moreover, the mild K1 decrease led to significant increases in both dichlorofluorescein (DCF) and ethidium signals -two indicators of oxidative stress -in the cells. Collectively, our findings have provided the first evidence indicating both a critical role of the K1 in maintaining the survival of melanoma cells and an important role of the K1 in modulating the oxidative stress state of the cells. These findings have exposed new functions of keratins in cancer cells, suggesting that K1 may become a novel therapeutic target for melanoma.

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Section: Discussionmentioning

confidence: 99%

A Mild Keratin 1 Decrease Leads to Cell Death and Increased Oxidative Stress in B16-F10 Melanoma Cell Lines

Zhang

Ying

2020

Preprint

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“…The inhibition of miR-927 was performed in C6/36 cells at 57 weeks of persistent infection with DENV-2 (C6-L57 cells) or in non-infected C6/36 cells using the miR-927 inhibitor (assay ID: MH17622) and miRNA inhibitor control number 1 as a non-related miRNA control. The miRNA-927 inhibitor is a chemically modified RNA complementary molecule that binds specifically to miR-927, preventing its binding to target mRNAs [26].…”

Section: Mir-927 Inhibition and Overexpression Assaysmentioning

confidence: 99%

miR-927 has pro-viral effects during acute and persistent infection with dengue virus type 2 in C6/36 mosquito cells

Avila-Bonilla

Yocupicio-Monroy

Marchat

et al. 2020

Journal of General Virology

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Dengue virus (DENV) is an important flavivirus that is transmitted to humans by Aedes mosquitoes, where it can establish a persistent infection underlying vertical and horizontal transmission. However, the exact mechanism of persistent DENV infection is not well understood. Recently miR-927 was found to be upregulated in C6/36-HT cells at 57 weeks of persistent infection (C6-L57), suggesting its participation during this type of infection. The aim of this study was to determine the role of miR-927 during infection with DENV type 2. The results indicate an overexpression of miR-927 in C6-L57 cells and acutely infected cells according to the time of infection and the m.o.i. used. The downregulation of miR-927 in C6-L57 cells results in a reduction of both viral titre and viral genome copy number. The overexpression of miR-927 in C6-L40 and C6/36 cells infected at an m.o.i. of 0.1 causes an increase in both viral titre and viral genome copy number, suggesting a pro-viral activity of miR-927. In silico prediction analysis reveals target mRNAs for miR-927 are implicated in post-translational modifications (SUMO), translation factors (eIF-2B), the innate immune system (NKIRAS), exocytosis (EXOC-2), endocytosis (APM1) and the cytoskeleton (FLN). The expression levels of FLN were the most affected by both miR-927 overexpression and inhibition, and FLN was determined to be a direct target of miR-927 by a dual-luciferase gene reporter assay. FLN has been associated with the regulation of the Toll pathway and either overexpression or downregulation of miR-927 resulted in expression changes of antimicrobial peptides (Cecropins A and G, and Defensin D) involved in the Toll pathway response.

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“…Manipulation of the expression levels of mRNAs targeting intracellular pathways involved in physiologic and/or pathologic processes might represent novel powerful therapeutic treatment options [ 159 , 160 ]. A snapshot of the current developmental status of targets of miRNA- and RBP-based modulators and connected therapeutics and their targets in MDS and sAML is summarized in Table 4 .…”

Section: Treatment Options Of Mrna Binding Modulators In Mds Andmentioning

confidence: 99%

“…However, it is encouraging that the first small-interfering RNA (siRNA) drug Onpattro ® (patisiran), a therapy for the rare hereditary disease transthyretin-mediated amyloidosis in adult patients, was approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) [ 196 , 197 ]. Furthermore, a number of miRNA vaccine therapies are currently in the clinical development or in phase I/II trials, while others were halted due to severe side effects [ 159 ]. The possibilities in the implementation of miRNAs as treatment option are rapidly progressing in a wide range of diseases alone or in combinations with other therapeutic agents affecting genetic and epigenetic targets.…”

Section: Therapeutic Possibilities Of Mirnas In Mds and Samlmentioning

confidence: 99%

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

Bauer

Vaxevanis

Heimer

et al. 2020

IJMS

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Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly differ to de novo acute myeloid leukemia (AML). Within these disorders, the spectrum of cytogenetic alterations and oncogenic mutations, the extent of a predisposing defective osteohematopoietic niche, and the irregularity of the tumor microenvironment is highly diverse. However, the exact underlying pathophysiological mechanisms resulting in hematopoietic failure in patients with MDS and sAML remain elusive. There is recent evidence that the post-transcriptional control of gene expression mediated by microRNAs (miRNAs), long noncoding RNAs, and/or RNA-binding proteins (RBPs) are key components in the pathogenic events of both diseases. In addition, an interplay between RBPs and miRNAs has been postulated in MDS and sAML. Although a plethora of miRNAs is aberrantly expressed in MDS and sAML, their expression pattern significantly depends on the cell type and on the molecular make-up of the sample, including chromosomal alterations and single nucleotide polymorphisms, which also reflects their role in disease progression and prediction. Decreased expression levels of miRNAs or RBPs preventing the maturation or inhibiting translation of genes involved in pathogenesis of both diseases were found. Therefore, this review will summarize the current knowledge regarding the heterogeneity of expression, function, and clinical relevance of miRNAs, its link to molecular abnormalities in MDS and sAML with specific focus on the interplay with RBPs, and the current treatment options. This information might improve the use of miRNAs and/or RBPs as prognostic markers and therapeutic targets for both malignancies.

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RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs

Cited by 282 publications

References 204 publications

A Mild Keratin 1 Decrease Leads to Cell Death and Increased Oxidative Stress in B16-F10 Melanoma Cell Lines

A Mild Keratin 1 Decrease Leads to Cell Death and Increased Oxidative Stress in B16-F10 Melanoma Cell Lines

miR-927 has pro-viral effects during acute and persistent infection with dengue virus type 2 in C6/36 mosquito cells

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

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