scholarly journals A tumor suppressive long noncoding RNA, DRAIC, inhibits protein translation and induces autophagy by activating AMPK

2021 ◽  
Author(s):  
Shekhar Saha ◽  
Ying Zhang ◽  
Briana Wilson ◽  
Roger Abounader ◽  
Anindya Dutta
Keyword(s):  
Signal Transduction ◽  
Noncoding Rna ◽  
Target Gene ◽  
Protein Translation ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Castration Resistant ◽  
Downstream Effects

LncRNAs are long RNA transcripts that do not code for proteins and that have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA which is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-κB pathway by inhibiting the IκBαkinase. Decreased DRAIC expression predicted poor patient outcome in gliomas and seven other cancers. We now report that DRAIC suppresses invasion, migration, colony formation and xenograft growth of glioblastoma derived cell lines. DRAIC activates AMPK by downregulating the NF-κB target gene GLUT1, and thus represses mTOR, leading to downstream effects such as decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis: the NF-κB pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-κB, protein translation and autophagy by the same lncRNA explains the tumor suppressive role of DRAIC in different cancers and reinforces the importance of lncRNAs as emerging regulators of signal transduction pathways.

scholarly journals A tumor suppressive long noncoding RNA, DRAIC, inhibits protein translation and induces autophagy by activating AMPK

2021 ◽  
Author(s):  
Shekhar Saha ◽  
Ying Zhang ◽  
Briana Wilson ◽  
Roger Abounader ◽  
Anindya Dutta
Keyword(s):  
Signal Transduction ◽  
Noncoding Rna ◽  
Protein Translation ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Castration Resistant ◽  
Iκb Kinase ◽  
Downstream Effects

LncRNAs are long RNA transcripts that do not code for proteins and that have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA which is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-kB pathway by inhibiting the IκB kinase. Decreased DRAIC expression predicted poor patient outcome in gliomas and seven other cancers. We now report that DRAIC suppresses invasion, migration, colony formation and xenograft growth of glioblastoma derived cell lines. DRAIC activates AMPK by downregulating the NF-κB target gene GLUT1, and thus represses mTOR, leading to downstream effects such as decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis: the NF-κB pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-κB, protein translation and autophagy by the same lncRNA explains the tumor suppressive role of DRAIC in different cancers and reinforces the importance of lncRNAs as emerging regulators of signal transduction pathways.

The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Extracellular Matrix ◽  
Inflammatory Reaction ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Translation ◽  
Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

scholarly journals Evidence for a positive role of PtdIns5P in T-cell signal transduction pathways

FEBS Letters ◽  
2010 ◽  
Vol 584 (11) ◽  
pp. 2455-2460 ◽  
Author(s):  
Geoffrey Guittard ◽  
Eva Mortier ◽  
Hélène Tronchère ◽  
Guylène Firaguay ◽  
Audrey Gérard ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Signal Transduction Pathways ◽  
Positive Role ◽  
Cell Signal ◽  
Cell Signal Transduction

Role of Tiam 1 in Rac-Mediated Signal Transduction Pathways

1996 ◽  
pp. 253-265 ◽  
Author(s):  
J. G. Collard ◽  
G. G. M. Habets ◽  
F. Michiels ◽  
J. Stam ◽  
R. A. van der Kammen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways

Fluoride mobilizes intracellular calcium and promotes Ca2+ influx in rat proximal tubules

1991 ◽  
Vol 261 (2) ◽  
pp. F318-F327 ◽  
Author(s):  
J. H. Dominguez ◽  
J. G. Garcia ◽  
J. K. Rothrock ◽  
D. English ◽  
C. Mann
Keyword(s):  
Signal Transduction ◽  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
G Protein ◽  
Pertussis Toxin ◽  
Time Course ◽  
Proximal Tubules ◽  
Signal Transduction Pathways ◽  
Pi Hydrolysis

In the renal proximal tubule, external Ca2+ ([Ca2+]o) is required for parathyroid hormone to elevate cytosolic Ca2+ ([Ca2+]i). However, other hormones increase [Ca2+]i in the absence of [Ca2+]o. These differences may arise from a diversity of signal transduction pathways acting on external and internal Ca2+ pools. However, Ca2+ influx may be necessary to expedite and maintain the rise of [Ca2+]i for a period after the initial surge. In this study, F- was used to probe the roles of intracellular Ca2+ mobilization, Ca2+ influx, and phosphoinositide (PI) hydrolysis on the surge of [Ca2+]i in rat proximal tubules. In the presence of external Ca2+; 1-20 mM F- evoked incremental rises of [Ca2+]i in tubules loaded with aequorin. Whereas 10 mM F- increased [Ca2+]i in the absence of [Ca2+]o, the time constant for the [Ca2+]i surge was increased. These findings are consistent with a role of Ca2+ influx on the effect of F- on [Ca2+]i. Indeed, 10 mM F- also enhanced the uptake of 45Ca2+, and promoted Ca2+ influx in aequorin- and fura-2-loaded, Ca(2+)-deprived tubules. In tubules, F- also activated PI hydrolysis with a time course that paralleled Ca2+ mobilization. The effect of F- on [Ca2+]i was not altered when the 39-kDa pertussis toxin substrate was inactivated with the toxin. This G protein was most likely Gi, because prostaglandin E2, an activator of Gi in tubules, dissociated the pertussis toxin-sensitive protein. The results support the notion that activation of a signal-transduction complex, the F- substrate, causes Ca2+ influx, mobilizes internal Ca2+, and activates PI hydrolysis in rat proximal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Oxidation Impacts the Intracellular Signaling Machinery in Hematological Disorders

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 353
Author(s):  
Elena Tibaldi ◽  
Enrica Federti ◽  
Alessandro Matte ◽  
Iana Iatcenko ◽  
Anand B. Wilson ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Conformational Changes ◽  
Intracellular Signaling ◽  
Signal Transduction Pathways ◽  
Functional Connection ◽  
Intracellular Signaling Pathway ◽  
Hematological Disorders ◽  
Dynamic Coordination ◽  
Transduction Mechanisms

The dynamic coordination between kinases and phosphatases is crucial for cell homeostasis, in response to different stresses. The functional connection between oxidation and the intracellular signaling machinery still remains to be investigated. In the last decade, several studies have highlighted the role of reactive oxygen species (ROS) as modulators directly targeting kinases, phosphatases, and downstream modulators, or indirectly acting on cysteine residues on kinases/phosphatases resulting in protein conformational changes with modulation of intracellular signaling pathway(s). Translational studies have revealed the important link between oxidation and signal transduction pathways in hematological disorders. The intricate nature of intracellular signal transduction mechanisms, based on the generation of complex networks of different types of signaling proteins, revealed the novel and important role of phosphatases together with kinases in disease mechanisms. Thus, therapeutic approaches to abnormal signal transduction pathways should consider either inhibition of overactivated/accumulated kinases or homeostatic signaling resetting through the activation of phosphatases. This review discusses the progress in the knowledge of the interplay between oxidation and cell signaling, involving phosphatase/kinase systems in models of globally distributed hematological disorders.

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