RNA-Targeted Therapies and High-Throughput Screening Methods

Zhu, Shaojun; Rooney, Saul; Michlewski, Gracjan

doi:10.3390/ijms21082996

Cited by 25 publications

(19 citation statements)

References 191 publications

(283 reference statements)

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“…In this final chapter we will focus on small molecules and chemistry-based strategies to target OSCC-associated RBPs. We will not discuss other genetic or non-genetic option, e.g., gene therapy, small interfering RNA (siRNA), circular RNAs, aptamers, or RNA-targeted therapies, which were recently discussed elsewhere [ 188 , 189 ].…”

Section: Therapeutic Targeting Options For Rbps Involved In Oral Cmentioning

confidence: 99%

“…This can be achieved either via targeting the RNA or the RBP directly. RNA-targeting strategies, which include nucleotide-based agents that target unstructured regions of RNA as well as small molecules that bind directly to structured RNAs are showing promising clinical success and have been discussed elsewhere [ 188 , 224 , 225 ]. In contrast, RBP-targeting approaches remain largely underdeveloped.…”

Section: Therapeutic Targeting Options For Rbps Involved In Oral Cmentioning

confidence: 99%

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RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

Weiße

Rosemann

Krauspe

et al. 2020

IJMS

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Nearly 7.5% of all human protein-coding genes have been assigned to the class of RNA-binding proteins (RBPs), and over the past decade, RBPs have been increasingly recognized as important regulators of molecular and cellular homeostasis. RBPs regulate the post-transcriptional processing of their target RNAs, i.e., alternative splicing, polyadenylation, stability and turnover, localization, or translation as well as editing and chemical modification, thereby tuning gene expression programs of diverse cellular processes such as cell survival and malignant spread. Importantly, metastases are the major cause of cancer-associated deaths in general, and particularly in oral cancers, which account for 2% of the global cancer mortality. However, the roles and architecture of RBPs and RBP-controlled expression networks during the diverse steps of the metastatic cascade are only incompletely understood. In this review, we will offer a brief overview about RBPs and their general contribution to post-transcriptional regulation of gene expression. Subsequently, we will highlight selected examples of RBPs that have been shown to play a role in oral cancer cell migration, invasion, and metastasis. Last but not least, we will present targeting strategies that have been developed to interfere with the function of some of these RBPs.

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Section: Therapeutic Targeting Options For Rbps Involved In Oral Cmentioning

confidence: 99%

Section: Therapeutic Targeting Options For Rbps Involved In Oral Cmentioning

confidence: 99%

RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

Weiße

Rosemann

Krauspe

et al. 2020

IJMS

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“…The RNA binding domain (RBD) is a region of RBP, which has been experimentally or structurally con rmed to directly bind RNA [8].Meanwhile, a large number of studies have recently reported the role of abnormal RNA metabolism and RNA processing, alternative splicing in various diseases, including cancer development [28,29].These results further con rm that RBP can affect the growth and metastasis of tumor cells by regulating various biological processes (such as RNA metabolism and RNA processing, RNA transport, RNA degradation).…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of the Functions and Prognostic Values of Rna Binding Protein in Head and Neck Squamous Cell Carcinoma

Song

Liu

et al. 2020

Preprint

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Background: Dysregulation of RNA-binding proteins (RBPs) playsan important role in controlling processes in cancer development.However, the function of RBPs has not been thoroughly and systematically documented in head and neck cancer.We aim to explore the role of RPB in the pathogenesis of HNSC.Methods: We obtained HNSC gene expression data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and the GEO databases, andidentified aberrantly expressed RBPs between tumors and normal tissues.Meanwhile, we performed a series of bioinformatics to explore the function and prognostic value of these RBPs.Results: A total of 249 abnormally expressed RBPs were identified, including 101 down-regulated RBPs and 148 up-regulated RBPs.Using least absolute shrinkage and selection operator (LASSO) and univariate Cox regression analysis, the fifteen RPBs were identified as hub genes. With the fifteen RPBS, the prognostic prediction model was constructed.Further analysis showed that the high-risk score of the patients expressed a better survival outcome. The prediction model was validated in another HNSC dataset, and similar findings were observed. Conclusions: Our results provide novel insights into the pathogenesis of HNSC. The fifteen RBP gene signature exhibited the predictive value of moderate HNSC prognosis, and have potential application value in clinical decision-making and individualized treatment.

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“…ASOs are relatively short, chemically modified single-stranded nucleic acid sequences that selectively pair to specific regions of mRNA resulting in endonucleolytic cleavage and degradation (Cosmi, 2016;DeVos & Miller, 2013;Heestermans & van Vlijmen, 2017;Kole, Krainer, & Altman, 2012) (Table 1). Currently over 60 ASO therapies are in, or have completed phase I/II trials (S. Zhu, Rooney, & Michlewski, 2020), with a substantial number of anti-thrombotic ASO therapeutics currently under development (Table 2).…”

Section: Contact System As Novel Target For Anticoagulation Therapymentioning

confidence: 99%

A novel rationale for targeting FXI: Insights from the hemostatic miRNA targetome for emerging anticoagulant strategies

Nourse

Danckwardt

2018

Preprint

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The treatment and prevention of thrombosis is currently under a period of rapid change with the replacement of traditional anticoagulant vitamin K antagonists with direct oral anticoagulants (DOACs), which specifically target factors FXa or FIIa.Nevertheless therapeutic targeting of blood coagulation is an inherently difficult task as it interferes with the delicate balance of pro-and anticoagulant activities. Although anticoagulants are employed in millions of thrombophilic patients worldwide each year, for a growing population with comorbidities who exhibit an increased risk of bleeding with DOAC treatment satisfying therapeutic options are still lacking and the quest for novel therapeutics continues.Recently the targeting of factors FXI and FXII have emerged as new therapeutic strategies. As these factors play an important roles in thrombosis, however are more or less functionally dispensable for hemostasis, they may potentially overcoming the functional obstacle of treating or preventing thrombosis without affecting hemostasis.A key question in following up this approach is which of these two factors is likely to be the more reliable target? Here we present and discuss a hitherto unrecognized rationale for the therapeutic targeting of FXI. This is based on mimicking endogenous FXI gene expression control by therapeutic delivery of miRNA mimics.Studies are urgently needed to test this therapeutic principle in a clinical setting. This is particularly applicable in hemostaseology where monitoring of therapeutic effects remains a daily routine and thus assessment of the efficacy and safety of such therapeutic components could be simply implemented ushering in a novel therapeutic era with broad applicability.

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RNA-Targeted Therapies and High-Throughput Screening Methods

Cited by 25 publications

References 191 publications

RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

Systematic Analysis of the Functions and Prognostic Values of Rna Binding Protein in Head and Neck Squamous Cell Carcinoma

A novel rationale for targeting FXI: Insights from the hemostatic miRNA targetome for emerging anticoagulant strategies

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