Experientia supplementum (2012)最新文献

Breast cancer remains one of the leading causes of cancer-related death among women worldwide, characterized by significant molecular and metabolic heterogeneity. Metabolic reprogramming has been shown to enable tumor cells to adapt to the dynamic microenvironment, supporting uncontrolled proliferation and survival. Emerging evidence highlights the critical roles of noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, in coordinating the complex regulatory networks underlying metabolic reprogramming in breast cancer. These ncRNAs influence key metabolic pathways such as glycolysis, lipid metabolism, and amino acid metabolism by targeting transcription factors, enzymes, and signaling cascades. Evidence suggests that targeting dysregulated ncRNAs holds significant potential for modulating cancer cell metabolism and offers novel strategies for breast cancer management. Furthermore, bioactive compounds derived from dietary sources have demonstrated the ability to modulate ncRNA expression and function, presenting exciting prospects for dietary or nutritional interventions in breast cancer therapy. This chapter compiles the intricate relationship between ncRNAs and metabolic reprogramming in breast cancer, with a focus on innovative techniques to target ncRNAs and the potential of dietary strategies to influence these regulatory pathways.

Noncoding RNAs (ncRNAs) are RNA molecules, which play critical roles in regulating gene expression and cellular activities, influencing processes like differentiation, proliferation, and cell survival, unlike messenger RNAs (mRNAs) that act as templates for protein production. Examples of ncRNAs include small interfering RNAs (siRNAs), microRNAs (miRNAs), ribosomal RNAs, transfer RNAs, small nucleolar RNAs (sno RNAs), and small nuclear RNAs (snRNAs). Small interfering RNAs (siRNAs) are a type of noncoding RNA that function primarily by silencing specific genes through a process called RNA interference (RNAi), in which they bind to complementary messenger RNA (mRNA) molecules, causing their degradation and preventing the translation of that mRNA into protein; essentially, they act as a "gene silencing" mechanism by targeting and destroying specific transcripts. In this chapter, we review the biogenesis, functions, and role of RNAs (siRNAs), in cancer research and role in therapy. siRNA (small interfering RNA) denotes small interfering RNA, consisting of 21-25 nucleotides. Discovery of siRNA (small interfering RNA) has been a significant breakthrough in biology. Small interfering RNAs (siRNAs) are single-stranded RNAs that are formed by the cleavage of longer double-stranded RNAs by the enzyme DICER1 within the RISC loading complex, which includes DICER1, an Argonaute protein, and either TARBP2 or PRKRA (PACT). Small interfering RNA (siRNA) is essential for health as it serves as a natural gene silencing tool, controlling gene expression posttranscriptionally, and is involved in several cellular processes such as development, immune response, and stress response; however, when not regulated properly, siRNAs may lead to diseases like cancer and viral infections, positioning them as a promising therapeutic target for targeted gene silencing therapies. siRNAs play a pivotal role in RNA interference (RNAi), a natural cellular process where they degrade complementary mRNA targets, preventing protein synthesis. This gene silencing mechanism has proven to be a valuable tool for controlling gene expression in research and therapeutic contexts. In cancer, siRNAs offer a promising approach to selectively silence oncogenes or other genes involved in tumor progression, thus hindering the development and spread of malignancies. However, the therapeutic potential of siRNAs faces several challenges, including efficient delivery to target cells, off-target effects, and stability issues. This chapter focuses on the biogenesis and functional significance of siRNAs, exploring their roles in cancer research and their promising therapeutic potential. With the continued advancement of RNA-based technologies, siRNAs hold considerable promise as a powerful tool for cancer treatment, offering new avenues for targeted therapies and personalized medicine.

Cancer is a genomically complex and multifaceted disease. Wealth of information distilled through decades of high-throughput research has revealed a broad spectrum of oncogenic signaling cascades, immunological evasion, and drug resistance, which play a steering role in carcinogenesis and metastasis. Noncoding RNAs have also emerged as key players in the regulation of multiple stages of cancer progression and metastatic spread of cancer cells to secondary sites. The concept of probiotics has started to gain limelight due to its ability to pharmacologically modulate the host microbiome and the immunological responses. The genomics era has provided impetus for the discovery and characterization of bacterial probiotic effector molecules that stimulate specific responses. We have witnessed an exponential increase in the seminal studies which provided proof-of-concept about the mechanistic regulation of cell signaling pathways and noncoding RNAs by probiotics. These exciting and groundbreaking studies ignited an outburst of data generated using several "omics" technologies. In this chapter, we have provided a summary of seminal studies associated with the anticancer and antimetastatic role of probiotics in animal models. However, circumstantial evidence has also underlined tumor-promoting role of probiotics in animal model studies. Therefore, there is a need to scrupulously reinterpret the existing pieces of evidence related to conflicting data about pro-tumorigenic and tumor-inhibitory roles of probiotics. We also critically summarized how probiotics modulated noncoding RNAs to prevent/inhibit cancer progression. Surprisingly, probiotics-mediated regulation of noncoding RNAs has not been comprehensively explored in different cancers. In accordance with this approach, in-depth analysis of target long noncoding RNAs and circular RNAs by probiotics will allow the researchers to develop near-to-complete signaling landscape to reap the full benefits of the medicinal significance of probiotics.

The clinical potential of noncoding RNA has proven to have major advancements recently. Understanding their mechanisms and biological functions drives the use of ncRNAs in clinical applications. ncRNAs play crucial roles in regulating all cellular processes by influencing key proteins involved in the singling pathways, both at gene transcriptional and translational levels. Additionally, ncRNAs can be detected intracellularly and extracellularly in different body fluids such as blood, urine, and cerebrospinal fluid, facilitating their noninvasive use in clinical settings. Several clinical trials have investigated ncRNAs' therapeutic and diagnostic use, leading to models that mimic the mechanistic functions of dysregulated ncRNAs. These models have provided new clinical tools for early disease diagnosis and therapy. While the FDA has approved some ncRNA-based diagnostic/therapeutic applications, other clinical trials were withdrawn or terminated. Challenges associated with ncRNAs include off-target effects due to a lack of specificity, decreased stability of specific ncRNAs in vivo, low cellular uptake, and limitations in delivery systems. Additionally, most exciting studies focus primarily on some types of ncRNA, such as microRNAs, highlighting the need for broader research into investigating other types of ncRNAs. Unlocking the full potential of ncRNAs will pave the way for a myriad of possibilities for developing novel strategies for early diagnosis, disease prognosis, and targeted therapies for different human diseases.

Mitochondria are key players in regulating cellular metabolism. Short noncoding RNAs, or microRNAs (miRNAs), have become significant modulators of gene expression and cellular functions. Recent research has demonstrated the presence and activity of mitochondrial miRNAs (MitomiRs) in various cell types, including blood cells. The role of MitomiRNAs in metabolic reprogramming throughout blood cell formation, including their biosynthesis, function, and possible therapeutic implications, was discussed in this chapter. The discovery of mitochondrial microRNAs (MitomiRs) transformed our understanding of gene regulation in these critical organelles. These MitomiRs were discovered as they were influencing mitochondrial gene expression, with considerable effects on various cellular functions like oxidative stress responses, production of energy, and apoptosis during blood cell development.

In the past, the vast genomic DNA, encoding transcripts now known as noncoding RNAs were considered as "junk DNA." However, over the years, studies have demonstrated the critical roles of these noncoding RNAs in various biological functions, leading to a major transformation in our understanding of molecular biology. Noncoding RNAs (ncRNAs) have emerged as critical players in the regulation of gene expression, cellular processes, and the maintenance of genomic stability. It is the complex interplay of the RNA diversity rather than the number of proteins that seems to have a significant role in the developmental complexity of organisms. This chapter provides an in-depth exploration of various categories of ncRNAs, their biogenesis, mechanisms of action, and implications in health and disease. With technological advancements in genomic sequencing and bioinformatics, our understanding of ncRNAs has expanded significantly, revealing their vast potential as therapeutic targets and biomarkers.

Small, endogenous noncoding RNAs known as miRNAs are widely distributed and use posttranscriptional control to suppress the expression of target genes. miRNAs have crucial roles in the development of disease and carcinogenesis, and new research suggests that miRNAs might be reliable diseases biomarkers. The identification of miRNAs in bodily fluids, in particular, has created a compelling possibility for the creation of noninvasive biomarkers for disease diagnosis, prognosis, and response prediction to treatment. Deregulation of the expression of microRNAs, which are essential for the regulation of several biological processes, has been connected to the emergence of metabolic, cardiovascular, neurodegenerative, and cancerous disorders. An exhaustive, up-to-date, and comprehensive investigation of the role of miRNAs in disease is presented in this chapter. Its goal is to stimulate further study in this field since small miRNAs may be utilized for effective disease detection, prognosis, and therapy.

For a long time, noncoding RNAs (ncRNAs) were considered irrelevant fragments of the genome, dismissed as genetic noise. However, recent breakthroughs have unveiled their crucial Role in regulating gene expression, influencing fundamental biological processes such as chromatin remodeling, epigenetic modifications, and cellular communication. Among them, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have drawn considerable attention due to their strong association with neurodegenerative disorders and cardiovascular diseases (CVDs). Despite their apparent differences, these conditions share molecular regulatory networks that ncRNAs help orchestrate. LncRNAs, like ANRIL and MEG3, play a Role in vascular integrity and cardiac fibrosis, while MIAT and MALAT1 are implicated in heart failure and ischemic injury. In Alzheimer's disease, BACE1-AS and BC200 contribute to the buildup of amyloid plaques and tau protein tangles, worsening cognitive decline. The ability of ncRNAs to act as molecular sponges-binding to miRNAs and modulating gene expression-demonstrates their intricate Role in disease progression. With advances in sequencing technologies and computational biology, ncRNAs are emerging as promising biomarkers and therapeutic targets. New approaches, including CRISPR-based gene editing and RNA therapeutics, present exciting possibilities for intervention. However, challenges such as stability, precise delivery, and potential side effects must be addressed before these treatments can be translated into clinical practice. This chapter delves into the expanding field of ncRNA research, highlighting its potential to reshape the future of precision medicine and targeted therapies.

Drug resistance hinders cancer treatment and directly affects cancer outcome and survival rate. While drug resistance is one of the worst features of cancers, there is limited knowledge about its mechanism and initiation in cancers. Noncoding RNAs are one of the most impactful epigenetic elements that are deregulated in many diseases. There is a strong correlation between cancers and noncoding RNAs. In this regard, we tried to find the connection between cancers and this epigenetic factor. In our investigation, we find an axis in which circular RNA, a dominant type of noncoding RNA, could regulate miRNA to control mRNA degradation. We encountered many deregulated pathways and tried to explain the mechanism underlying the CirRNA/miRNA/mRNA axis in drug resistance of cancer, including the most widely recognized resistance type of cancer in the body.

In recent years, noncoding RNAs have sparked significant interest in understanding the diverse roles of ncRNAs in cellular regulation and disease processes. Noncoding RNAs (ncRNAs), encompassing small noncoding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs), are critical regulators of gene expression, epigenetic modifications, and various cellular processes within the human genome. The diverse nature ncRNAs, along with certain complex features, has made them difficult to study through traditional experimental methods. As a result, bioinformatics tools have expanded the possibilities for offering new insights through advanced computational strategies. This chapter explores the recent advancements in ncRNA databases, emphasizing their importance and the innovative in silico strategies that enable the prediction and analysis of biological interactions, particularly for miRNAs and lncRNAs. It offers an in-depth overview of the structural properties, classification, and functions of various types of noncoding RNAs, highlighting their crucial roles in cellular processes. Additionally, the chapter discusses the significant therapeutic potential of ncRNAs, focusing on their applications in treating cancer and other severe diseases. These insights are pivotal in advancing the development of targeted therapies and precision medicine.