scholarly journals Targeting circular RNAs as a therapeutic approach: current strategies and challenges

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Alina T. He ◽  
Jinglei Liu ◽  
Feiya Li ◽  
Burton B. Yang
Keyword(s):  
Therapeutic Approach ◽  
High Specificity ◽  
Circular Rna ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Cellular Processes ◽  
Specific Manner ◽  
Recent Developments ◽  
A Cell ◽  
Cell Type Specific

AbstractSignificant progress has been made in circular RNA (circRNA) research in recent years. Increasing evidence suggests that circRNAs play important roles in many cellular processes, and their dysregulation is implicated in the pathogenesis of various diseases. CircRNAs are highly stable and usually expressed in a tissue- or cell type-specific manner. Therefore, they are currently being explored as potential therapeutic targets. Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies, respectively. These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems. Furthermore, recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner. While still in the early stages of development, the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency. In this review, we describe circRNA properties and functions and highlight their significance in disease. We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach. Lastly, we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.

scholarly journals Rel Induces Interferon Regulatory Factor 4 (IRF-4) Expression in Lymphocytes

2000 ◽  
Vol 191 (8) ◽  
pp. 1281-1292 ◽  
Author(s):  
Raelene J. Grumont ◽  
Steve Gerondakis
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Nuclear Factor Κb ◽  
Wild Type ◽  
Cell Type ◽  
Regulatory Factor ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific ◽  
Interferon Regulatory Factor 4

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel−/− B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel−/− B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor κB can repress the transcription of IFN-regulated genes in a cell type–specific manner.

PLAG1 enhances the stemness profiles of acinar cells in normal human salivary glands in a cell type-specific manner

2020 ◽  
Vol 62 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Yuriko Goto ◽  
Miho Ibi ◽  
Hirotaka Sato ◽  
Junichi Tanaka ◽  
Rika Yasuhara ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Acinar Cells ◽  
Cell Type ◽  
Specific Manner ◽  
A Cell ◽  
Normal Human ◽  
Cell Type Specific

scholarly journals NFKB1 and Cancer: Friend or Foe?

Cells ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 133 ◽  
Author(s):  
Julia Concetti ◽  
Caroline L Wilson
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Multiple Roles ◽  
Current Evidence ◽  
Cellular Processes ◽  
Specific Manner ◽  
Organ Specific ◽  
A Cell ◽  
Potential Cancer

Current evidence strongly suggests that aberrant activation of the NF-κB signalling pathway is associated with carcinogenesis. A number of key cellular processes are governed by the effectors of this pathway, including immune responses and apoptosis, both crucial in the development of cancer. Therefore, it is not surprising that dysregulated and chronic NF-κB signalling can have a profound impact on cellular homeostasis. Here we discuss NFKB1 (p105/p50), one of the five subunits of NF-κB, widely implicated in carcinogenesis, in some cases driving cancer progression and in others acting as a tumour-suppressor. The complexity of the role of this subunit lies in the multiple dimeric combination possibilities as well as the different interacting co-factors, which dictate whether gene transcription is activated or repressed, in a cell and organ-specific manner. This review highlights the multiple roles of NFKB1 in the development and progression of different cancers, and the considerations to make when attempting to manipulate NF-κB as a potential cancer therapy.

Abstract LB-028: Cell density sensing alters TGF-beta signaling in a cell type-specific manner, independent from Hippo pathway activation

2015 ◽  
Author(s):  
Flore Nallet-Staub ◽  
Xueqian Yin ◽  
Cristèle Gilbert ◽  
Véronique Marsaud ◽  
Saber Ben Mimoun ◽  
...  
Keyword(s):  
Cell Density ◽  
Hippo Pathway ◽  
Tgf Beta ◽  
Cell Type ◽  
Pathway Activation ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific

Limitations of the Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) Models for Chronobiological Investigations

2019 ◽  
Vol 34 (6) ◽  
pp. 634-644 ◽  
Author(s):  
Arthur H. Cheng ◽  
Samuel W. Fung ◽  
Hai-Ying Mary Cheng
Keyword(s):  
Confounding Factor ◽  
The Body ◽  
Mouse Strains ◽  
Extreme Caution ◽  
Specific Manner ◽  
A Cell ◽  
Peripheral Clocks ◽  
Cell Type Specific ◽  
Encoding Gene ◽  
The Impact

The principal circadian pacemaker in mammals, the suprachiasmatic nucleus (SCN), expresses a number of neuropeptides that facilitate intercellular synchrony, helping to generate coherent outputs to peripheral clocks throughout the body. In particular, arginine vasopressin (AVP)– and vasoactive intestinal peptide (VIP)–expressing neurons have been recognized as crucial subpopulations within the SCN and have thus been the focus of many chronobiological studies. Here, we analyze the neuropeptide expression of 2 popular transgenic mouse strains commonly used to direct or restrict Cre-mediated recombination to AVP- and VIP-ergic neurons. The Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) “driver” mouse strains express the Cre recombinase under the control of the endogenous Avp or Vip gene, respectively, allowing scientists either to ablate their gene of interest or to overexpress a transgene in a cell type–specific manner. Although these are potentially very powerful tools for chronobiologists and other scientists studying AVP- and VIP-ergic neurons, we found that neuropeptide expression in these mice is significantly decreased when an IRES(2)-Cre cassette is inserted downstream of the neuropeptide-encoding gene locus. The impact of IRES(2)-Cre cassette insertion on neuropeptide expression may be a confounding factor in many experimental designs. Our findings suggest that extreme caution must be exercised when using these mouse models to avoid misinterpretation of empirical results.

scholarly journals Fibronectin signals through integrin α5β1 to regulate cardiovascular development in a cell type-specific manner

2015 ◽  
Vol 407 (2) ◽  
pp. 195-210 ◽  
Author(s):  
Dongying Chen ◽  
Xia Wang ◽  
Dong Liang ◽  
Julie Gordon ◽  
Ashok Mittal ◽  
...  
Keyword(s):  
Cardiovascular Development ◽  
Cell Type ◽  
Integrin Α5β1 ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific
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