Potential of microRNAs as novel targets in the alleviation of pathological fear

Murphy, Conor P.; Singewald, Nicolas

doi:10.1111/gbb.12427

Cited by 16 publications

(11 citation statements)

References 104 publications

(131 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…microRNAs (miRNAs or miRs), a class of small non-coding RNAs of 19–25 nucleotides in length, are believed to regulate gene expression by binding miRNAs to the 3′untranslated region (3′UTR) of mRNAs, thereby leading to mRNA degradation or blocking of mRNA translation [[9], [10], [11], [12]]. It has been estimated that over 30% of human genes are regulated by miRNAs [13,14].…”

Section: Introductionmentioning

confidence: 99%

A miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance in gastric cancer

Zhang

Yao

et al. 2019

eBioMedicine

View full text Add to dashboard Cite

Background Gastric cancer (GC) ranks the fifth most common cancer, and chemotherapy is one of the most common treatments for GC. However, chemoresistance limits the effectiveness of chemotherapy and leads to treatment failure. This study aims to investigate the biological effect of miR-567 on gastric tumourigenesis and chemoresistance and reveal the possible mechanism. Methods We measured the expression of miR-567 in 37 paired normal and stomach tumour specimens, as well as GC cell lines by Real-time PCR. The functional effects of miR-567 were validated using in vitro and in vivo assays. Dual-luciferase report assays and Chromatin immunoprecipitation (ChIP) assay were conducted for target evaluation, western blot assay was used to confirm the relationships. Findings Our data showed that miR-567 was downregulated in gastric tissues and gastric cancer cells compared with normal tissues and gastric epithelial cells. In vitro , Gain- and lose-of-function assays showed miR-567 not only weakened cells proliferative ability, but also sensitized GC cells to 5-FU and oxaliplatin. In vivo , miR-567 overexpression significantly repressed the tumourigenesis of GC cells compared with the vector control. Mechanistic analysis showed that PIK3AP1 activated AKT phosphorylation in GC. Meanwhile, miR-567 directly targeted PIK3AP1 to inactivate PI3K/AKT/c-Myc pathway and c-Myc inversely regulated miR-567 expression, thus forming a miR-567-PIK3AP1- PI3K/AKT-c-Myc feedback loop explaining the function of miR-567. Interpretation Our studies revealed that miR-567 acts as a tumour suppressor gene and suppresses GC tumorigenesis and chemoresistance via a miR-567-PIK3AP1- PI3K/AKT-c-Myc feedback loop. These results suggest that miR-567 may serve as a target for chemoresistance and a potential prognostic biomarker for GC.

show abstract

Section: Introductionmentioning

confidence: 99%

A miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance in gastric cancer

Zhang

Yao

et al. 2019

eBioMedicine

View full text Add to dashboard Cite

show abstract

“…The mechanisms by which the expression of genes are fine-tuned to, in turn, shape extinction is an emerging area that has also led to a focus on microRNAs (miRNAs) (Murphy and Singewald 2018 )—a class of short, single-stranded non-coding RNAs (Smith and Kenny 2017 ). A pioneering study on this subject showed that extinction training increased the microRNA, miR-128b, to cause expression of a set of genes which are associated with synaptic plasticity.…”

Section: It Is (Not) All In the Genes: Genetic Models Of Impaired Extmentioning

confidence: 99%

Rodent models of impaired fear extinction

Singewald

Holmes

2018

Psychopharmacology

Self Cite

View full text Add to dashboard Cite

The measurement of Pavlovian forms of fear extinction offers a relatively simple behavioral preparation that is nonetheless tractable, from a translational perspective, as an approach to study mechanisms of exposure therapy and biological underpinnings of anxiety and trauma-related disorders such as post-traumatic stress disorder (PTSD). Deficient fear extinction is considered a robust clinical endophenotype for these disorders and, as such, has particular significance in the current “age of RDoC (research domain criteria).” Various rodent models of impaired extinction have thus been generated with the objective of approximating this clinical, relapse prone aberrant extinction learning. These models have helped to reveal neurobiological correlates of extinction circuitry failure, gene variants, and other mechanisms underlying deficient fear extinction. In addition, they are increasingly serving as tools to investigate ways to therapeutically overcome poor extinction to support long-term retention of extinction memory and thus protection against various forms of fear relapse; modeled in the laboratory by measuring spontaneous recovery, reinstatement and renewal of fear. In the current article, we review models of impaired extinction built around (1) experimentally induced brain region and neural circuit disruptions (2) spontaneously-arising and laboratory-induced genetic modifications, or (3) exposure to environmental insults, including stress, drugs of abuse, and unhealthy diet. Collectively, these models have been instrumental in advancing in our understanding of extinction failure and underlying susceptibilities at the neural, genetic, molecular, and neurochemical levels; generating renewed interest in developing novel, targeted and effective therapeutic treatments for anxiety and trauma-related disorders.

show abstract

“…Sleep disturbance is common in people with fear-related anxiety disorders. It has been shown that some microRNAs, such as miR-132 and miR-144-3p, play an important role both in generation of fear and in suppression of memories of it and are associated with consolidation and reconsolidation of LTM, respectively (Murphy, Singewald, 2018). At the same time, impaired miR-132 expression is observed during sleep deprivation and is accompanied by cognitive dysfunctions (Karabulut et al, 2019).…”

Section: Micrornas Long-term Memory and Sleepmentioning

confidence: 99%

The role of microRNAs in learning and long-term memory

Grinkevich

2020

Vestn. VOGiS

View full text Add to dashboard Cite

The mechanisms of long-term memory formation and ways to improve it (in the case of its impairment) remain an extremely difficult problem yet to be solved. Over the recent years, much attention has been paid to microRNAs in this regard. MicroRNAs are unique endogenous non-coding RNAs about 22 nucleotides in length; each can regulate translation of hundreds of messenger RNA targets, thereby controlling entire gene networks. MicroRNAs are widely represented in the central nervous system. A large number of studies are currently being conducted to investigate the role of microRNAs in the brain functioning. A number of microRNAs have been shown to be involved in the process of synaptic plasticity, as well as in the long-term memory formation. Disruption of microRNA biogenesis leads to significant cognitive dysfunctions. Moreover, impaired microRNA biogenesis is one of the causes of the pathogenesis of mental disorders, neurodegenerative illnesses and senile dementia, which are often accompanied by deterioration in the learning ability and by memory impairment. Optimistic predictions are made that microRNAs can be used as targets for therapeutic treatment and for diagnosing the above pathologies. The importance of applications related to microRNAs significantly raises interest in studying their functions in the brain. Thus, this review is focused on the role of microRNAs in cognitive processes. It describes microRNA biogenesis and the role of miRNAs in the regulation of gene expression, as well as the latest achievements in studying the functional role of microRNAs in learning and in long-term memory formation, depending on the activation or inhibition of their expression. The review presents summarized data on the effect of impaired microRNA biogenesis on long-term memory formation, including those associated with sleep deprivation. In addition, analysis is provided of the current literature related to the prospects of improving cognitive processes by influencing microRNA biogenesis via the use of CRISPR/Cas9 technologies and active mental and physical exercises.

show abstract

Potential of microRNAs as novel targets in the alleviation of pathological fear

Cited by 16 publications

References 104 publications

A miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance in gastric cancer

A miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance in gastric cancer

Rodent models of impaired fear extinction

The role of microRNAs in learning and long-term memory

Contact Info

Product

Resources

About