Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.

The use of non-coding RNAs (ncRNAs) as drug targets is being researched due to their discovery and their role in disease. Targeting ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), is an attractive approach for treating various diseases, such as cardiovascular disease and cancer. This seminar discusses the current status of ncRNAs as therapeutic targets in different pathological conditions. Regarding miRNA-based drugs, this approach has made significant progress in preclinical and clinical testing for cardiovascular diseases, where the limitations of conventional pharmacotherapy are evident. The challenges of miRNA-based drugs, including specificity, delivery, and tolerability, will be discussed. New approaches to improve their success will be explored. Furthermore, it extensively discusses the potential development of targeted therapies for cardiovascular disease. Finally, this document reports on the recent advances in identifying and characterizing microRNAs, manipulating them, and translating them into clinical applications. It also addresses the challenges and perspectives towards clinical application.

[Research progress of non-coding RNA involved in glycolysis regulation of hepatocellular carcinoma].

Liver cancer is a common tumor of digestive system. Hepatocellular carcinoma (HCC) is a common type of liver cancer, which has a high degree of malignancy and ranks among the top causes of cancer-related death in the world. Metabolic reprogramming is considered to be an important marker of carcinogenesis. Glucose metabolism is one of the main ways for cells to produce energy. Glycolysis, as the basic reaction of glucose metabolism, plays an important role in cell metabolism. Therefore, the regulation of glycolysis is of great significance to the proliferation and evolution of tumors. More and more non-coding RNAs (ncRNA) have been proved to play an important role in the regulation of tumor glycolysis. This article reviews the role of ncRNA in the regulation of HCC glycolysis and its related mechanisms. At the same time, the prospect of targeted therapy for HCC based on the related mechanisms of glycolysis regulation is put forward.

Comprehensive review for non-coding RNAs: From mechanisms to therapeutic applications.

Non-coding RNAs (ncRNAs) are an assorted collection of transcripts that are not translated into proteins. Since their discovery, ncRNAs have gained prominence as crucial regulators of various biological functions across diverse cell types and tissues, and their abnormal functioning has been implicated in disease. Notably, extensive research has focused on the relationship between microRNAs (miRNAs) and human cancers, although other types of ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as significant contributors to human disease. In this review, we provide a comprehensive summary of our current knowledge regarding the roles of miRNAs, lncRNAs, and circRNAs in cancer and other major human diseases, particularly cancer, cardiovascular, neurological, and infectious diseases. Moreover, we discuss the potential utilization of ncRNAs as disease biomarkers and as targets for therapeutic interventions.

Exploring the Key Signaling Pathways and ncRNAs in Colorectal Cancer.

Colorectal cancer (CRC) is the third most prevalent cancer to be diagnosed, and it has a substantial mortality rate. Despite numerous studies being conducted on CRC, it remains a significant health concern. The disease-free survival rates notably decrease as CRC progresses, emphasizing the urgency for effective diagnostic and therapeutic approaches. CRC development is caused by environmental factors, which mostly lead to the disruption of signaling pathways. Among these pathways, the Wingless/Integrated (Wnt) signaling pathway, Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, Mitogen-Activated Protein Kinase (MAPK) signaling pathway, Transforming Growth Factor-ß (TGF-ß) signaling pathway, and p53 signaling pathway are considered to be important. These signaling pathways are also regulated by non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They have emerged as crucial regulators of gene expression in CRC by changing their expression levels. The altered expression patterns of these ncRNAs have been implicated in CRC progression and development, suggesting their potential as diagnostic and therapeutic targets. This review provides an overview of the five key signaling pathways and regulation of ncRNAs involved in CRC pathogenesis that are studied to identify promising avenues for diagnosis and treatment strategies.

Exploring ncRNA-mediated regulation of EGFR signalling in glioblastoma: From mechanisms to therapeutics.

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway.

Extracellular vesicles as carriers for noncoding RNA-based regulation of macrophage/microglia polarization: an emerging candidate regulator for lung and traumatic brain injuries.

Macrophage/microglia function as immune defense and homeostatic cells that originate from bone marrow progenitor cells. Macrophage/microglia activation is historically divided into proinflammatory M1 or anti-inflammatory M2 states based on intracellular dynamics and protein production. The polarization of macrophages/microglia involves a pivotal impact in modulating the development of inflammatory disorders, namely lung and traumatic brain injuries. Recent evidence indicates shared signaling pathways in lung and traumatic brain injuries, regulated through non-coding RNAs (ncRNAs) loaded into extracellular vesicles (EVs). This packaging protects ncRNAs from degradation. These vesicles are subcellular components released through a paracellular mechanism, constituting a group of nanoparticles that involve exosomes, microvesicles, and apoptotic bodies. EVs are characterized by a double-layered membrane and are abound with proteins, nucleic acids, and other bioactive compounds. ncRNAs are RNA molecules with functional roles, despite their absence of coding capacity. They actively participate in the regulation of mRNA expression and function through various mechanisms. Recent studies pointed out that selective packaging of ncRNAs into EVs plays a role in modulating distinct facets of macrophage/microglia polarization, under conditions of lung and traumatic brain injuries. This study will explore the latest findings regarding the role of EVs in the progression of lung and traumatic brain injuries, with a specific focus on the involvement of ncRNAs within these vesicles. The conclusion of this review will emphasize the clinical opportunities presented by EV-ncRNAs, underscoring their potential functions as both biomarkers and targets for therapeutic interventions.

Role of non-coding RNAs mediated pyroptosis on cancer therapy: a review.

INTRODUCTION: Non-coding RNAs (ncRNAs), which are incapable of encoding proteins, are involved in the progression of numerous tumors by altering transcriptional and post-transcriptional processing. Recent studies have revealed prominent features of ncRNAs in pyroptosis, a type of non-apoptotic programmed cellular destruction linked to an inflammatory reaction. Drug resistance has arisen gradually as a result of anti-apoptotic proteins, therefore strategies based on pyroptotic cell death have attracted increasing attention. We have observed that ncRNAs may exert significant influence on cancer therapy, chemotherapy, radio- therapy, targeted therapy and immunotherapy, by regulating pyroptosis. AREAS COVERED: Literatures were searched (December 2023) for studies on cancer therapy for ncRNAs-mediated pyroptotic cell death. EXPERT OPINION: The most universal mechanical strategy for ncRNAs to regulate target genes is competitive endogenous RNAs (ceRNA). Besides, certain ncRNAs could directly interact with proteins and modulate downstream genes to induce pyroptosis, resulting in tumor growth or inhibition. In this review, we aim to display that ncRNAs, predominantly long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), could function as potential biomarkers for diagnosis and prognosis and produce new insights into anti-cancer strategies modulated by pyroptosis for clinical applications.

From powerhouse to regulator: The role of mitoepigenetics in mitochondrion-related cellular functions and human diseases.

Beyond their crucial role in energy production, mitochondria harbor a distinct genome subject to epigenetic regulation akin to that of nuclear DNA. This paper delves into the nascent but rapidly evolving fields of mitoepigenetics and mitoepigenomics, exploring the sophisticated regulatory mechanisms governing mitochondrial DNA (mtDNA). These mechanisms encompass mtDNA methylation, the influence of non-coding RNAs (ncRNAs), and post-translational modifications of mitochondrial proteins. Together, these epigenetic modifications meticulously coordinate mitochondrial gene transcription, replication, and metabolism, thereby calibrating mitochondrial function in response to the dynamic interplay of intracellular needs and environmental stimuli. Notably, the dysregulation of mitoepigenetic pathways is increasingly implicated in mitochondrial dysfunction and a spectrum of human pathologies, including neurodegenerative diseases, cancer, metabolic disorders, and cardiovascular conditions. This comprehensive review synthesizes the current state of knowledge, emphasizing recent breakthroughs and innovations in the field. It discusses the potential of high-resolution mitochondrial epigenome mapping, the diagnostic and prognostic utility of blood or tissue mtDNA epigenetic markers, and the promising horizon of mitochondrial epigenetic drugs. Furthermore, it explores the transformative potential of mitoepigenetics and mitoepigenomics in precision medicine. Exploiting a theragnostic approach to maintaining mitochondrial allostasis, this paper underscores the pivotal role of mitochondrial epigenetics in charting new frontiers in medical science.

Noncoding RNAs in B cell non-Hodgkins lymphoma.

B-cell non-Hodgkins lymphomas (BCNHLs) are a category of B-cell cancers that show heterogeneity. These blood disorders are derived from different levels of B-cell maturity. Among NHL cases, ∼80-90 % are derived from B-cells. Recent studies have demonstrated that noncoding RNAs (ncRNAs) contribute to almost all parts of mechanisms and are essential in tumorigenesis, including B-cell non-Hodgkins lymphomas. The study of ncRNA dysregulations in B-cell lymphoma unravels important mysteries in lymphoma's molecular etiology. It seems also necessary for discovering novel trials as well as investigating the potential of ncRNAs as markers for their diagnosis and prognosis. In the current study, we summarize the role of ncRNAs involving miRNAs, long noncoding RNAs, as well as circular RNAs in the development or progression of BCNHLs.

Non-Coding RNAs: Novel Regulators of Macrophage Homeostasis in Ocular Vascular Diseases.

Ocular neovascularization can impair vision and threaten patients' quality of life. However, the underlying mechanism is far from transparent. In all mammals, macrophages are a population of cells playing pivotal roles in the innate immune system and the first line of defense against pathogens. Therefore, it has been speculated that the disfunction of macrophage homeostasis is involved in the development of ocular vascular diseases. Moreover, various studies have found that non-coding RNAs (ncRNAs) regulate macrophage homeostasis. This study reviewed past studies of the regulatory roles of ncRNAs in macrophage homeostasis in ocular vascular diseases.

Two effective factors in cancer: Investigating the effect of ncRNAs in cancer and also the effect of nanotherapy in its treatment.

Cancer remains one of the most pressing health challenges globally, necessitating ongoing research into innovative therapeutic approaches. This article explores two critical factors influencing cancer: ncRNAs and nanotherapy. The role of ncRNAs, including microRNAs and long non-coding RNAs, in cancer pathogenesis, progression, and treatment resistance is elucidated. Additionally, the potential of nanotherapy, leveraging nanoscale materials for targeted drug delivery and enhanced therapeutic efficacy, is investigated. By comprehensively analyzing the molecular mechanisms underlying ncRNA dysregulation and the promise of nanotherapy in cancer treatment, this article aims to provide valuable insights into novel therapeutic strategies for combating cancer.

Critical role of exosome, exosomal non-coding RNAs and non-coding RNAs in head and neck cancer angiogenesis.

Head and neck cancer (HNC) refers to the epithelial malignancies of the upper aerodigestive tract. HNCs have a constant yet slow-growing rate with an unsatisfactory overall survival rate globally. The development of new blood vessels from existing blood conduits is regarded as angiogenesis, which is implicated in the growth, progression, and metastasis of cancer. Aberrant angiogenesis is a known contributor to human cancer progression. Representing a promising therapeutic target, the blockade of angiogenesis aids in the reduction of the tumor cells oxygen and nutrient supplies. Despite the promise, the association of existing anti-angiogenic approaches with severe side effects, elevated cancer regrowth rates, and limited survival advantages is incontrovertible. Exosomes appear to have an essential contribution to the support of vascular proliferation, the regulation of tumor growth, tumor invasion, and metastasis, as they are a key mediator of information transfer between cells. In the exocrine region, various types of noncoding RNAs (ncRNAs) identified to be enriched and stable and contribute to the occurrence and progression of cancer. Mounting evidence suggest that exosome-derived ncRNAs are implicated in tumor angiogenesis. In this review, the characteristics of angiogenesis, particularly in HNC, and the impact of ncRNAs on HNC angiogenesis will be outlined. Besides, we aim to provide an insight on the regulatory role of exosomes and exosome-derived ncRNAs in angiogenesis in different types of HNC.

Targeting non-coding RNAs and N6-methyladenosine modification in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most common form of primary liver cancers, accounts for a significant portion of cancer-related death globally. However, the molecular mechanisms driving the onset and progression of HCC are still not fully understood. Emerging evidence has indicated that non-protein-coding regions of genomes could give rise to transcripts, termed non-coding RNA (ncRNA), forming novel functional driving force for aberrant cellular activity. Over the past decades, overwhelming evidence has denoted involvement of a complex array of molecular function of ncRNAs at different stages of HCC tumorigenesis and progression. In this context, several pre-clinical studies have highlighted the potentials of ncRNAs as novel therapeutic modalities in the management of human HCC. Moreover, N6-methyladenosine (m6A) modification, the most prevalent form of internal mRNA modifications in mammalian cells, is essential for the governance of biological processes within cells. Dysregulation of m6A in ncRNAs has been implicated in human carcinogenesis, including HCC. In this review, we will discuss dysregulation of several hallmark ncRNAs (miRNAs, lncRNAs, and circRNAs) in HCC and address the latest advances for their involvement in the onset and progression of HCC. We also focus on dysregulation of m6A modification and various m6A regulators in the etiology of HCC. In the end, we discussed the contemporary preclinical and clinical application of ncRNA-based and m6A-targeted therapies in HCC.

Empowering Graph Neural Networks with Block-Based Dual Adaptive Deep Adjustment for Drug Resistance-Related NcRNA Discovery.

Drug resistance to chemotherapeutic agents remains a formidable challenge in cancer treatment, significantly impacting treatment efficacy. Extensive research has exposed the intimate involvement of noncoding RNAs (ncRNAs) in conferring resistance to cancer drugs. Understanding the intricate associations between ncRNAs and drug resistance is of pivotal importance in advancing clinical interventions and expediting drug development. However, traditional biological experimental methods are hampered by limitations, such as labor intensiveness, time consumption, and constraints in scalability. Addressing these challenges necessitates the development of efficient computational methods for the accurate prediction of potential ncRNA-drug resistance associations (NDRA). However, most existing predictive models primarily focus on known ncRNA-drug resistance associations, often neglecting the critical aspect of similarity information between ncRNAs and drug resistance. This oversight may hinder the accuracy of characterizing these associations. To overcome the limitations of existing computational models, we proposed B-NDRA, a computational framework designed for the discovery of drug resistance-related ncRNA. Initially, we constructed a heterogeneous graph that integrates ncRNA-drug resistance pairs, leveraging both known associations and similarity fusion information between ncRNAs and drug resistance. Subsequently, we employed an attention mechanism to aggregate local features of graph nodes following a dimensionality reduction of node features. Further, a graph neural network (GNN) facilitated the learning of global node embeddings. Notably, the integration of dual adaptive deep adjustment architectures, encompassing intrablock and interblock methodologies, enabled efficient extraction of global features while balancing local and global features. Finally, B-NDRA employed a multilayer perceptron to predict associations between ncRNAs and drug resistance. Through rigorous 5-fold cross-validation, B-NDRA achieved average AUC, AUPR, Accuracy, Precision, Recall, and F1-score values of 92.2%, 91.9%, 84.88%, 86.9%, 82.37%, and 84.44%, respectively. Furthermore, comparative evaluations were conducted on established models, namely, GAEMDA, GRPAMDA, and LRGCPND. The results, obtained through three distinct 5-fold cross-validation strategies, demonstrated a notable performance improvement across almost all metrics for our B-NDRA. Specific case studies targeting Doxorubicin and Imatinib further validated the practicality of our B-NDRA in discovering potential NDRA. These results confirm the potential of our B-NDRA as a valuable tool in advancing cancer research and therapeutic development. The source code and data set of B-NDRA can be found at https://github.com/XuanLi1145/B-NDRA.

A bibliometric analysis of non-coding RNA studies in acute pancreatitis.

BACKGROUND: Non-coding RNA (ncRNA) is a type of RNA that does not code for proteins and plays a crucial role in the onset, progression, diagnosis, and therapy of acute pancreatitis. However, bibliometric, and visual analyses of studies on acute pancreatitis and ncRNA are lacking. This study seeks to provide a bibliometric overview of the knowledge structure and research hotspots of ncRNA in the field of acute pancreatitis research. MATERIALS AND METHODS: Literature search and collection of information in the field of ncRNA-related research in acute pancreatitis from 2000-2023 through the Web of Science Core Collection. Use CiteSpace and VOSviewer to visually analyze countries, institutions, authors, and keywords. RESULTS: A total of 563 articles have been published in the field of ncRNA-related research in acute pancreatitis, and the number of publications in this field is gradually increasing. The largest number of publications was from China. Four clusters were produced by the co-occurrence cluster analysis of the top 89 keywords: studies of ncRNA in inflammation, autophagy, and apoptosis in acute pancreatitis; studies related to microRNA expression in pancreatic cancer among ncRNA; studies related to microRNAs as diagnostic and therapeutic markers in acute pancreatitis; and studies related to ncRNA in acute pancreatitis; The key words "injury," "pathway" and "extracellular vesicles" are the key words of emerging research hotspots. CONCLUSION: In conclusion, ncRNA research in acute pancreatitis is an established discipline. Researchers can use the research hotspots and frontiers in this field as a guide for choosing their research direction.

Unraveling the cross-talk between N6-methyladenosine modification and non-coding RNAs in breast cancer: Mechanisms and clinical implications.

In recent years, breast cancer (BC) has surpassed lung cancer as the most common malignant tumor worldwide and remains the leading cause of cancer death in women. The etiology of BC usually involves dysregulation of epigenetic mechanisms and aberrant expression of certain non-coding RNAs (ncRNAs). N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, widely exists in ncRNAs to affect its biosynthesis and function, and is an important regulator of tumor-related signaling pathways. Interestingly, ncRNAs can also regulate or target m6A modification, playing a key role in cancer progression. However, the m6A-ncRNAs regulatory network in BC has not been fully elucidated, especially the regulation of m6A modification by ncRNAs. Therefore, in this review, we comprehensively summarize the interaction mechanisms and biological significance of m6A modifications and ncRNAs in BC. Meanwhile, we also focused on the clinical application value of m6A modification in BC diagnosis and prognosis, intending to explore new biomarkers and potential therapeutic targets.

Deciphering chemoresistance in osteosarcoma: Unveiling regulatory mechanisms and function through the lens of noncoding RNA.

Osteosarcoma (OS) is a primary malignant bone tumor and is prevalent in children, adolescents, and elderly individuals. It has the characteristics of high invasion and metastasis. Neoadjuvant chemotherapy combined with surgical resection is the most commonly used treatment for OS. However, the efficacy of OS is considerably diminished by chemotherapy resistance. In recent years, noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, are hot topics in the field of chemotherapy resistance research. Several studies have demonstrated that ncRNAs are substantially associated with chemoresistance in OS. Thus, the present study overviews the abnormally expressed ncRNAs in OS and the molecular mechanisms involved in chemoresistance, with an emphasis on their function in promoting or inhibiting chemoresistance. ncRNAs are expected to become potential therapeutic targets for overcoming drug resistance and predictive biomarkers in OS, which are of great significance for enhancing the therapeutic effect and improving the prognosis.

LINC00909 up-regulates pluripotency factors and promotes cancer stemness and metastasis in pancreatic ductal adenocarcinoma by targeting SMAD4.

BACKGROUND: Pancreatic cancer stem cells are crucial for tumorigenesis and cancer metastasis. Presently, long non-coding RNAs were found to be associated with Pancreatic Ductal Adenocarcinoma stemness characteristics but the underlying mechanism is largely known. Here, we aim to explore the function of LINC00909 in regulating pancreatic cancer stemness and cancer metastasis. METHODS: The expression level and clinical characteristics of LINC00909 were verified in 80-paired normal pancreas and Pancreatic Ductal Adenocarcinoma tissues from Guangdong Provincial People's Hospital cohort by in situ hybridization. RNA sequencing of PANC-1 cells with empty vector or vector encoding LINC00909 was experimented for subsequent bioinformatics analysis. The effect of LINC00909 in cancer stemness and metastasis was examined by in vitro and in vivo experiments. The interaction between LINC00909 with SMAD4 and the pluripotency factors were studied. RESULTS: LINC00909 was generally upregulated in pancreatic cancer tissues and was associated with inferior clinicopathologic features and outcome. Over-expression of LINC00909 enhanced the expression of pluripotency factors and cancer stem cells phenotype, while knock-down of LINC00909 decreased the expression of pluripotency factors and cancer stem cells phenotype. Moreover, LINC00909 inversely regulated SMAD4 expression, knock-down of SMAD4 rescued the effect of LINC00909-deletion inhibition on pluripotency factors and cancer stem cells phenotype. These indicated the effect of LINC00909 on pluripotency factors and CSC phenotype was dependent on SMAD4 and MAPK/JNK signaling pathway, another downstream pathway of SMAD4 was also activated by LINC00909. Specifically, LINC00909 was localized in the cytoplasm in pancreatic cancer cells and decreased the stability the SMAD4 mRNA. Finally, we found over-expression of LINC00909 not only accelerated tumor growth in subcutaneous mice models, but also facilitated tumorigenicity and spleen metastasis in orthotopic mice models. CONCLUSION: We demonstrate LINC00909 inhibits SMAD4 expression at the post-transcriptional level, which up-regulates the expression of pluripotency factors and activates the MAPK/JNK signaling pathway, leading to enrichment of cancer stem cells and cancer metastasis in pancreatic cancer.