Writers, readers, and erasers RNA modifications and drug resistance in cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

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In Search of a Function for the N6-Methyladenosine in Epitranscriptome, Autophagy and Neurodegenerative Diseases

Neurology International, Journal Year: 2023, Volume and Issue: 15(3), P. 967 - 979

Published: Aug. 10, 2023

Changes in epitranscriptome with N6-methyladenine (m6A) modification could be involved the development of multiple diseases, which might a prevalent messenger RNAs (mRNAs) eukaryotes. The m6A performed through action methyltransferases, demethylases, and methylation-binding proteins. Importantly, methylation may associated various neurological disorders including Alzheimer’s disease (AD), Parkinson’s (PD), depression, aging-related and/or aging itself. In addition, functionally regulate eukaryotic transcriptome by influencing splicing, export, subcellular localization, translation, stability, decay mRNAs. Neurodegenerative diseases possess wide variety phenotypes, depending on neurons that degenerate occasion. Interestingly, an increasing amount evidence has indicated modulate expression autophagy-related genes promote autophagy neuronal cells. Oxidative stresses such as reactive oxygen species (ROS) stimulate RNA methylation, also related to regulation neurodegenerative diseases. Both play critical roles regulating health condition neurons. Therefore, comprehensive understanding relationship human benefit developing therapeutic strategies future. This paper reviews advances regulatory mechanisms occurrence aging, discussing possible procedures autophagy.

Language: Английский

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Role of Post-Transcriptional Regulation in Learning and Memory in Mammals

Genes, Journal Year: 2024, Volume and Issue: 15(3), P. 337 - 337

Published: March 5, 2024

After many decades, during which most molecular studies on the regulation of gene expression focused transcriptional events, it was realized that post-transcriptional control equally important in order to determine where and when specific proteins were be synthesized. Translational is importance brain, all steps mRNA maturation, transport different regions cells actual expression, response signals, constitute basis for neuronal plasticity and, as a consequence, structural stabilization/modification synapses; notably, these latter events are fundamental highest brain functions, such learning memory, characterized by long-term potentiation (LTP) synapses. Here, we will discuss bases considering both role RNA-binding (RBPs) effects non-coding RNAs involved controlling splicing, editing, stability translation mRNAs. Importantly, has also been found dysregulation metabolism/localization pathological conditions, arising either development or adult nervous system.

Language: Английский

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The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3866 - 3866

Published: March 30, 2024

For much of human evolution, the average lifespan was <40 years, due in part to disease, infant mortality, predators, food insecurity, and, for females, complications childbirth. Thus, many females did not reach age menopause (45–50 years age) and it is mainly past several hundred that has been extended >75 primarily public health advances, medical interventions, antibiotics, nutrition. Therefore, underlying biological mechanisms responsible disease risk following must have evolved during complex processes leading Homo sapiens serve functions pre-menopausal state. Furthermore, as a primary function survival species effective reproduction, likely most advantages having such post-menopausal risks relate reproduction ability address environmental stresses. This opinion/perspective will be discussed context how could enhance with improved offspring, perhaps why are preserved. Not all exhibit this set diseases, those who do develop diseases conditions. The state operate unified complex, but independent variables, potential some overlap. there would heterogeneity if factors essential reproductive also concept sets reversible epigenetic changes associated puberty, pregnancy, lactation offered explain observations regarding distribution conditions their roles reproduction. While involvement an system dynamic “modification-demodification-remodification” paradigm contributing hypothesis at point, validation lead better understanding commonalities may future interventions control after menopause.

Language: Английский

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The role of N6-methyladenosine modification in rodent models of neuropathic pain: from the mechanism to therapeutic potential

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 166, P. 115398 - 115398

Published: Aug. 28, 2023

Neuropathic pain (NP) is a common chronic condition resulted from lesions or diseases of somatosensory nervous system, but the pathogenesis remains unclear. A growing body evidence supports relationship between and N6-methyladenosine (m6A) modifications RNA. However, studies on role m6A in NP are still at an early stage. Elucidating different etiologies important for understanding specific NP. This article provides comprehensive review methylation including methyltransferases ("writers"), demethylases ("erasers"), binding proteins ("readers") models. Further analysis pathogenic mechanism provided novel theoretical practical significance clinical treatment

Language: Английский

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Epitranscriptome Changes in Neurodegenerative Diseases and the Potential Strategy for the Therapeutics

Published: June 29, 2023

Changes in epitranscriptome with N6‐methyladenine (m6A) modification could be involved the development of multiple diseases, which might a prevalent messenger RNAs (mRNAs) eukaryotes. The m6A performed through action methyltransferases, demethylases, and methylation-binding proteins. Importantly, methylation may associated various neurological disorders including Alzheimer&#039;s disease (AD), Parkinson&#039;s (PD), depression, aging related and/or itself. In addition, functionally regulate eukaryotic transcriptome by influencing splicing, export, subcellular localization, translation, stability, decay mRNAs. Neurodegenerative diseases possess wide variety phenotypes depending on neurons that degenerate at occasions. Interestingly, increasing number evidences have indicated modulate expression autophagy-related genes promote autophagy neuronal cells. Oxidative stresses such as reactive oxygen species (ROS) stimulate RNA methylation, also to regulation neurodegenerative diseases. Both play critical roles regulating health condition neurons. Therefore, comprehensive understanding relationship human benefit developing therapeutic strategies future. This paper reviews advances regulatory mechanisms occurrence aging, discussing possible procedures autophagy.

Language: Английский

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Sex Determination in Homo sapiens as a Multi-Step Process: Potential for Development of Variants and Sex Differences in Disease Risk

Journal of Biomedical Science and Engineering, Journal Year: 2024, Volume and Issue: 17(01), P. 13 - 34

Published: Jan. 1, 2024

Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed prior humans. While chromosomal-specific approach has been successful strategy for survival large variety species including humans, fidelity sex determination leading 100% outcomes is not achieved many species, with evidence homosexual or bisexual behaviour evident more than 1500 species. Thus, such indicates that multi-step process single event, as such, could lead appearance variants during which developed much earlier Variants arise either due intrinsic variation steps determination, also be influenced by environmental factors biological psychological nature. In contrast do require interventions hormone therapy surgery, expression gender dysphoria, based psychology, but underpinnings can hormonal surgery. numbers those dysphoria small (~0.6% - 1.0% population), attention given this issue raises possibility impacting emergence some expressing dysphoria. Furthermore, transitioning from male-to-female female-to-male consequences regarding disease risks latter life, autoimmune diseases. This review will attempt discuss why potentially improved upon evolution, how potential role chromosome function on neurodevelopment may central commitment current likely integrated into other sex-related events puberty, pregnancy, menopause ensure survival. It contribute differences risk epigenetic modifications play risk.

Language: Английский

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Unveiling the role of RNA methylation in glioma: Mechanisms, prognostic biomarkers, and therapeutic targets

Cellular Signalling, Journal Year: 2024, Volume and Issue: 124, P. 111380 - 111380

Published: Sept. 3, 2024

Language: Английский

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