Search

Autophagy is a self-recycling and conserved process, in which the senescent cytoplasmic components are degraded in cells and then recycled to maintain homeostatic balance. Emerging evidence has suggested the involvement of autophagy in oncogenesis and progression of various cancers, such as ovarian cancer (OC). Meanwhile, the non-coding RNAs (ncRNAs) frequently regulate the mRNA transcription and other functional signaling pathways in cell autophagy, displaying promising roles in human cancer pathogenesis and therapeutic response. This article mainly reviews the cutting-edge research advances about the interactions between ncRNAs and autophagy in OC. This review not only summarizes the underlying mechanisms of dynamic ncRNA-autophagy association in OC, but also discusses their prognostic implications and therapeutic biomarkers. The aim of this review was to provide a more in-depth knowledge framework exploring the ncRNA-autophagy crosstalk and highlight the promising treatment strategies for OC patients. [ABSTRACT FROM AUTHOR]

Phosphorus (P) limitation in the majority of world soils is a major constraint for plant growth and crop productivity. RNA sequencing was used to discover novel P-responsive gene transcripts (PRGTs) in leaves and roots of Arabidopsis. Hisat StringTie and the Cufflinks TopHat transcript assembler were used to analyze reads and identify 1074 PRGTs with a >5-fold altered abundance during P limitation. Interestingly, 60% of these transcripts were not previously reported. Among the novel PRGTs, 106 were from unannotated genes, and some were among the most P-responsive, including At2g36727 which encodes a novel miRNA. Annotated novel PRGTs encode transcription factors, miRNAs, small signaling peptides, long non-coding RNAs, defense-related proteins, and transporters, along with proteins involved in many biological processes. We identified several genes that undergo alternative splicing during P limitation, including a novel miR399- resistant splice variant of PHOSPHATE2 (PHO2.2). Several novel P-responsive genes were regulated by PHOSPHATE STARVATION RESPONSE1 (PHR1), PHR1-LIKE 1 (PHL1), and PHO2. We discovered that P-limited plants show increased resistance to pathogens and drought stress mediated by PHR1–PHL1. Identification of novel P-responsive transcripts and the discovery of the influence of P limitation on biotic and abiotic stress adds a significant component to our understanding of plant P signaling. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide. Accumulating evidence suggests that persistent HPV infection is closely related to a subset of HNSCC types, and the incidence of human papillomavirus (HPV)-positive HNSCC has been annually increasing in recent decades. Although the carcinogenesis of HPV-positive HNSCC has not been completely elucidated, it has been well confirmed that E6 and E7, the main viral oncoproteins are responsible for the maintenance of malignant transformation, promotion of cell proliferation, and increase in tumor invasion. Moreover, compared with HPV-negative HNSCC, HPV-positive HNSCC shows some special clinical-pathological features, which are possibly related to HPV infection and their specific regulatory mechanisms. Non-coding RNA (ncRNA) is a class of RNA lacking the protein-coding function and playing a critical regulatory role via multiple complex molecular mechanisms. NcRNA is an important regulatory pattern of epigenetic modification, which can exert significant effects on HPV-induced tumorigenesis and progression by deregulating downstream genes. However, the knowledge of ncRNAs is still limited, hence, a better understanding of ncRNAs could provide some insights for exploring the carcinogenesis mechanism and identifying valuable biomarkers in HPV-positive HNSCC. Therefore, in this review, we mainly focused on the expression profile of ncRNAs (including lncRNA, miRNA, and circRNA) and explored their regulatory role in HPV-positive HNSCC, aiming to clarify the regulatory mechanism of ncRNAs and identify valuable biomarkers for HPVpositive HNSCC. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a major infectious disease induced by Mycobacterium tuberculosis (M. tb) which causes the world's dominant fatal bacterial contagious disease. Increasing studies have indicated that exosomes may be a novel option for the diagnosis and treatment of TB. Exosomes are nanovesicles (30-150 nm) containing lipids, proteins and non-coding RNAs (ncRNAs) released from various cells, and can transfer their cargos and communicate between cells. Furthermore, exosomal ncRNAs exhibit diagnosis potential in bacterial infections, including TB. Additionally, differential exosomal ncRNAs regulate the physiological and pathological functions of M. tb-infected cells and act as diagnostic markers for TB. This current review explored the potential biological roles and the diagnostic application prospects of exosomal ncRNAs, and included recent information on their pathogenic and therapeutic functions in TB. [ABSTRACT FROM AUTHOR]

Uterine leiomyomas (ULs), frequent benign tumours of the female reproductive tract, are associated with a range of symptoms and significant morbidity. Despite extensive research, there is no consensus on essential points of UL initiation and development. The main reason for this is a pronounced inter- and intratumoral heterogeneity resulting from diverse and complicated mechanisms underlying UL pathobiology. In this review, we comprehensively analyse risk and protective factors for UL development, UL cellular composition, hormonal and paracrine signalling, epigenetic regulation and genetic abnormalities. We conclude the need to carefully update the concept of UL genesis in light of the current data. Staying within the framework of the existing hypotheses, we introduce a possible timeline for UL development and the associated key events—from potential prerequisites to the beginning of UL formation and the onset of driver and passenger changes. [ABSTRACT FROM AUTHOR]

PIWI-interacting RNA (piRNA) is a class of recently discovered small non-coding RNA molecules with a length of 18–33 nt that interacts with the PIWI protein to form the piRNA/PIWI complex. The PIWI family is a subfamily of Argonaute (AGO) proteins that also contain the AGO family which bind to microRNA (miRNA). Recently studies indicate that piRNAs are not specific to in the mammalian germline, they are also expressed in a tissue-specific manner in a variety of human tissues and participated in various of diseases, such as cardiovascular, neurological, and urinary tract diseases, and are especially prevalent in malignant tumors in these systems. However, the functions and abnormal expression of piRNAs in respiratory tract diseases and their underlying mechanisms remain incompletely understood. In this review, we discuss current studies summarizing the biogenetic processes, functions, and emerging roles of piRNAs in respiratory tract diseases, providing a reference value for future piRNA research. [ABSTRACT FROM AUTHOR]

Background: The vast and promising class of long non-coding RNAs (lncRNAs) has been under investigation for distinct therapeutic applications. Nevertheless, their role as molecular drivers of bone regeneration remains poorly studied. The lncRNA H19 mediates osteogenic differentiation of Mesenchymal Stem/Stromal Cells (MSCs) through the control of intracellular pathways. However, the effect of H19 on the extracellular matrix (ECM) components is still largely unknown. This research study was designed to decode the H19-mediated ECM regulatory network, and to reveal how the decellularized siH19-engineered matrices influence MSC proliferation and fate. This is particularly relevant for diseases in which the ECM regulation and remodeling processes are disrupted, such as osteoporosis. Methods: Mass spectrometry-based quantitative proteomics analysis was used to identify ECM components, after oligonucleotides delivery to osteoporosis-derived hMSCs. Moreover, qRT-PCR, immunofluorescence and proliferation, differentiation and apoptosis assays were performed. Engineered matrices were decellularized, characterized by atomic force microscopy and repopulated with hMSC and pre-adipocytes. Clinical bone samples were characterized by histomorphometry analysis. Results: Our study provides an in-depth proteome-wide and matrisome-specific analysis of the ECM proteins controlled by the lncRNA H19. Using bone marrow-isolated MSC from patients with osteoporosis, we identified fibrillin-1 (FBN1), vitronectin (VTN) and collagen triple helix repeat containing 1 (CTHRC1), among others, as having different pattern levels following H19 silencing. Decellularized siH19-engineered matrices are less dense and have a decreased collagen content compared with control matrices. Repopulation with naïve MSCs promotes a shift towards the adipogenic lineage in detriment of the osteogenic lineage and inhibits proliferation. In pre-adipocytes, these siH19-matrices enhance lipid droplets formation. Mechanistically, H19 is targeted by miR-29c, whose expression is decreased in osteoporotic bone clinical samples. Accordingly, miR-29c impacts MSC proliferation and collagen production, but does not influence ALP staining or mineralization, revealing that H19 silencing and miR-29c mimics have complementary but not overlapping functions. Conclusion: Our data suggest H19 as a therapeutic target to engineer the bone ECM and to control cell behavior. [ABSTRACT FROM AUTHOR]

Anxiety-related disorders (ARDs) are chronic neuropsychological diseases and the sixth leading cause of disability in the world. As dysregulation of microRNAs (miRs) are observed in the pathological course of neuropsychiatric disorders, the present study aimed to introduce miRs that underlie anxiety processing in the brain. First, we collected the experimentally confirmed anxiety-related miRNAs (ARmiRs), predicted their target transcripts, and introduced critical cellular pathways with key commune hub genes. As a result, we have found nine anxiolytic and ten anxiogenic ARmiRs. The anxiolytic miRs frequently target the mRNA of Acyl-CoA synthetase long-chain family member 4 (Acsl4), AFF4-AF4/FMR2 family member 4 (Aff4), and Krüppel like transcription factor 4 (Klf4) genes, where miR-34b-5p and miR-34c-5p interact with all of them. Moreover, the anxiogenic miRs frequently target the mRNA of nine genes; among them, only two miR (miR-142-5p and miR-218-5p) have no interaction with the mRNA of trinucleotide repeat-containing adaptor 6B (Tnrc6b), and miR-124-3p interacts with all of them where MAPK is the main signaling pathway affected by both anxiolytic and anxiogenic miR. In addition, the anxiolytic miR commonly target E2F transcription factor 5 (E2F5) in the TGF-β signaling pathway, and the anxiogenic miR commonly target Ataxin 1 (Atxn1), WASP-like actin nucleation promoting factor (Wasl), and Solute Carrier Family 17 Member 6 (Slc17a6) genes in the notch signaling, adherence junction, and synaptic vesicle cycle pathways, respectively. Taken together, we conclude that the most important anxiolytic (miR-34c, Let-7d, and miR-17) and anxiogenic (miR-19b, miR-92a, and 218) miR, as hub epigenetic modulators, potentially influence the pathophysiology of anxiety, primarily via interaction with the MAPK signaling pathway. Moreover, the role of E2F5 as a novel putative target for anxiolytic miRNAs in ARDs disorders deserves further exploration. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) are on the rise in the world. Therefore, it is a critical issue to reveal the precise pathophysiological mechanisms and novel therapeutic strategies to deal with such conditions. Passing through different mechanisms, non-coding RNAs (ncRNAs) play a pivotal role in NDDs through various mechanisms, by changing the expression of some genes, interference with protein translation and alterations in some signaling pathways. It urges the need to introduce novel strategies and therapeutic agents with multi-targeting potentials. Phytochemicals are hopeful antioxidants and anti-inflammatory agents with promising modulatory roles on dysregulated signaling pathways and protein translation during NDDs. In this study, the role of ncRNAs (e.g. lncRNAs, miRNA, siRNAs and piRNAs) was highlighted in NDDs. This study also aimed to investigate the role of phytochemicals (phenolic compounds, alkaloids, terpenoids and sulfur compounds) in the modulation of ncRNAs during NDDs such as Alzheimer's disease, Parkinson's disease, epilepsy, depression and amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) are common chronic disorders associated with progressive nervous system damage, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, among others. Mitochondria are abundant in various nervous system cells and provide a bulk supply of the adenosine triphosphate necessary for brain function, considered the center of the free-radical theory of aging. One common feature of NDs is mitochondrial dysfunction, which is involved in many physiopathological processes, including apoptosis, inflammation, oxidative stress, and calcium homeostasis. Recently, genetic studies revealed extensive links between mitochondrion impairment and dysregulation of non-coding RNAs (ncRNAs) in the pathology of NDs. Traditional Chinese medicines (TCMs) have been used for thousands of years in treating NDs. Numerous modern pharmacological studies have demonstrated the therapeutic effects of prescription, herbal medicine, bioactive ingredients, and monomer compounds of TCMs, which are important for managing the symptoms of NDs. Some highly effective TCMs exert protective effects on various key pathological features regulated by mitochondria and play a pivotal role in recovering disrupted signaling pathways. These disrupted signaling pathways are induced by abnormally-expressed ncRNAs associated with mitochondrial dysfunction, including microRNAs, long ncRNAs, and circular RNAs. In this review, we first explored the underlying ncRNA mechanisms linking mitochondrial dysfunction and neurodegeneration, demonstrating the implication of ncRNA-induced mitochondrial dysfunction in the pathogenesis of NDs. The ncRNA-induced mitochondrial dysfunctions affect mitochondrial biogenesis, dynamics, autophagy, Ca2+ homeostasis, oxidative stress, and downstream apoptosis. The review also discussed the targeting of the disease-related mitochondrial proteins in NDs and the protective effects of TCM formulas with definite composition, standardized extracts from individual TCMs, and monomeric compounds isolated from TCM. Additionally, we explored the ncRNA regulation of mitochondrial dysfunction in NDs and the effects and potential mechanisms of representative TCMs in alleviating mitochondrial pathogenesis and conferring anti-inflammatory, antioxidant, and anti-apoptotic pathways against NDs. Therefore, this review presents an overview of the role of mitochondrion-related ncRNAs and the target genes for TCM-based therapeutic interventions in NDs, providing insight into understanding the "multi-level compound-target-pathway regulatory" treatment mechanism of TCMs. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new type of cell death characterized by damage to the intracellular microenvironment, which causes the accumulation of lipid hydroperoxide and reactive oxygen species to cause cytotoxicity and regulated cell death. Noncoding RNAs (ncRNAs) play an important role in gene expression at the epigenetic, transcriptional, and post-transcriptional levels through interactions with different DNAs, RNAs, or proteins. Increasing evidence has shown that ferroptosis-related ncRNAs are closely related to the occurrence and progression of several diseases, including urological malignancies. Recently, the role of ferroptosis-associated ncRNAs (long non-coding RNAs, micro RNAs, and circular RNAs) in the occurrence, drug resistance, and prognosis of urological malignancies has attracted widespread attention. However, this has not yet been addressed systematically. In this review, we discuss this issue as much as possible to expand the knowledge and understanding of urological malignancies to provide new ideas for exploring the diagnosis and treatment of urological malignancies in the future. Furthermore, we propose some challenges in the clinical application of ferroptosis-associated ncRNAs. [ABSTRACT FROM AUTHOR]

Endometriosis is a complex disorder that is characterized by the abnormal growth of endometrial-like tissue outside the uterus. It is associated with chronic inflammation, severe pelvic pain, infertility, and significantly reduced quality of life. Although the exact mechanism of endometriosis remains unknown, inflammation and altered immunity are considered key factors in the immunopathogenesis of the disorder. Disturbances of immune responses result in reduced clearance of regurgitated endometrial cells, which elicits oxidative stress and progression of inflammation. Proinflammatory mediators could affect immune cells’ recruitment, fate, and function. Reciprocally, the activation of immune cells can promote inflammation. Aberrant expression of non-coding RNA (ncRNA) in patient and animal lesions could be suggestive of their role in endometriosis establishment. The engagement of these RNAs in regulating diverse biological processes, including inflammatory responses and activation of inflammasomes, altered immunity, cell proliferation, migration, invasion, and angiogenesis are widespread and far-reaching. Therefore, ncRNAs can be identified as a determining candidate regulating the inflammatory responses and immune system. This review aims in addition to predict the role of ncRNAs in the immunopathogenesis of endometriosis through regulating inflammation and altered immunity based on previous studies, it presents a comprehensive view of inflammation role in the pathogenesis of endometriosis.

Pancreatic cancer (PC) is a serious gastrointestinal tract disease for which the 5-year survival rate is less than 10%, even in developed countries such as the USA. The genomic profile alterations and dysregulated biological mechanisms commonly occur in PC. Macroautophagy/autophagy is a cell death process that is maintained at a basal level in physiological conditions, whereas its level often changes during tumorigenesis. The function of autophagy in human cancers is dual and can be oncogenic and onco-suppressor. Autophagy is a potent controller of tumorigenesis in PC. The supportive autophagy in PC escalates the growth rate of PC cells and its suppression can mediate cell death. Autophagy also determines the metastasis of PC cells, and it can control the EMT in affecting migration. Moreover, starvation and hypoxia can stimulate glycolysis, and glycolysis induction can be mediated by autophagy in enhancing tumorigenesis in PC. Furthermore, protective autophagy stimulates drug resistance and gemcitabine resistance in PC cells, and its inhibition can enhance radiosensitivity. Autophagy can degrade MHC-I to mediate immune evasion and also regulates polarization of macrophages in the tumor microenvironment. Modulation of autophagy activity is provided by silibinin, ursolic acid, chrysin and huaier in the treatment of PC. Non-coding RNAs are also controllers of autophagy in PC and its inhibition can improve therapy response in patients. Moreover, mitophagy shows dysregulation in PC, which can enhance the proliferation of PC cells. Therefore, a bioinformatics analysis demonstrates the dysregulation of autophagy-related proteins and genes in PC as biomarkers.

Emerging evidence highlights the multifaceted roles of the RNA epitranscriptome during viral infections. By modulating the modification landscape of viral and host RNAs, viruses enhance their propagation and elude host surveillance mechanisms. Here, we discuss how specific RNA modifications, in either host or viral RNA molecules, impact the virus-life cycle and host antiviral responses, highlighting the potential of targeting the RNA epitranscriptome for novel antiviral therapies.

Renal cell carcinoma (RCC) represents a malignant tumor of the urinary system. Individuals with early-stage RCC could be cured by surgical treatment, but a considerable number of cases of advanced RCC progress to drug resistance. Recently, numerous reports have demonstrated that a variety of non-coding RNAs (ncRNAs) contribute to tumor occurrence and development. ncRNAs can act as oncogenic or tumor suppressor genes to regulate proliferation, migration, drug resistance and other processes in RCC cells through a variety of signaling pathways. Considering the lack of treatment options for advanced RCC after drug resistance, ncRNAs may be a good choice as biomarkers of drug resistance in RCC and targets to overcome drug resistance. In this review, we discussed the effects of ncRNAs on drug resistance in RCC and the great potential of ncRNAs as a biomarker of or a new therapeutic method in RCC.

Cardiovascular disease (CVD) is a major contributor to increasing morbidity and mortality worldwide and seriously threatens human health and life. Cardiomyocyte death is considered the pathological basis of various CVDs, including myocardial infarction, heart failure, and aortic dissection. Multiple mechanisms, such as ferroptosis, necrosis, and apoptosis, contribute to cardiomyocyte death. Among them, ferroptosis is an iron-dependent form of programmed cell death that plays a vital role in various physiological and pathological processes, from development and aging to immunity and CVD. The dysregulation of ferroptosis has been shown to be closely associated with CVD progression, yet its underlying mechanisms are still not fully understood. In recent years, a growing amount of evidence suggests that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs, and circular RNAs, are involved in the regulation of ferroptosis, thus affecting CVD progression. Some ncRNAs also exhibit potential value as biomarker and/or therapeutic target for patients with CVD. In this review, we systematically summarize recent findings on the underlying mechanisms of ncRNAs involved in ferroptosis regulation and their role in CVD progression. We also focus on their clinical applications as diagnostic and prognostic biomarkers as well as therapeutic targets in CVD treatment. Data availability: No new data were created or analyzed in this study. Data sharing is not applicable to this article.

After the metabolic syndrome and its components, thyroid disorders represent the most common endocrine disorders, with increasing prevalence in the last two decades. Thyroid dysfunctions are distinguished by hyperthyroidism, hypothyroidism, or inflammation (thyroiditis) of the thyroid gland, in addition to the presence of thyroid nodules that can be benign or malignant. Thyroid cancer is typically detected via an ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) and cytological examination of the specimen. This approach has significant limitations due to the small sample size and inability to characterize follicular lesions adequately. Due to the rapid advancement of high-throughput molecular biology techniques, it is now possible to identify new biomarkers for thyroid neoplasms that can supplement traditional imaging modalities in postoperative surveillance and aid in the preoperative cytology examination of indeterminate or follicular lesions. Here, we review current knowledge regarding biomarkers that have been reliable in detecting thyroid neoplasms, making them valuable tools for assessing the efficacy of surgical procedures or adjunctive treatment after surgery. We are particularly interested in providing an up-to-date and systematic review of emerging biomarkers, such as mRNA and non-coding RNAs, that can potentially detect thyroid neoplasms in clinical settings. We discuss evidence for miRNA, lncRNA and circRNA dysregulation in several thyroid neoplasms and assess their potential for use as diagnostic and prognostic biomarkers.

Background: Idiopathic pulmonary arterial hypertension (PAH) is a potentially fatal pulmonary vascular disease with an extremely poor natural course. The limitations of current treatment and the unclear etiology and pathogenesis of idiopathic PAH require new targets and avenues of exploration involved in the pathogenesis of PAH. tRNA-derived small RNAs (tsRNAs), a new type of small non-coding RNAs, have a significant part in the progress of diverse diseases. However, the potential functions behind tsRNAs in idiopathic PAH remain unknown.Methods: Small RNA microarray was implemented on three pairs of plasma of idiopathic PAH patients and healthy controls to investigate and compare tsRNAs expression profiles. Validation samples were used for real-time polymerase chain reaction (Real-time PCR) to verify several dysregulated tsRNAs. Bioinformatic analysis was adopted to determine potential target genes and mechanisms of the validated tsRNAs in PAH.Results: Microarray detected 816 statistically significantly dysregulated tsRNAs, of which 243 tsRNAs were upregulated and 573 were downregulated in PAH. Eight validated tsRNAs in the results of Real-time PCR were concordant with the small RNA microarray: four upregulated (tRF3a-AspGTC-9, 5’tiRNA-31-GluCTC-16, i-tRF-31:54-Val-CAC-1 and tRF3b-TyrGTA-4) and four downregulated (5’tiRNA-33-LysTTT-4, i-tRF-8:32-Val-AAC-2, i-tRF-2:30-His-GTG-1, and i-tRF-15:31-Lys-CTT-1). The Gene Ontology analysis has shown that the verified tsRNAs are related to cellular macromolecule metabolic process, regulation of cellular process, and regulation of cellular metabolic process. It is disclosed that potential target genes of verified tsRNAs are widely involved in PAH pathways by Kyoto Encyclopedia of Genes and Genomes.Conclusion: This study investigated tsRNA profiles in idiopathic PAH and found that the dysregulated tsRNAs may become a novel type of biomarkers and possible targets for PAH.

Diabetic cardiomyopathy (DCM) is defined as abnormalities in myocardial structure and function in the setting of diabetes and in the absence of cardiovascular diseases, such as coronary artery disease, hypertension, and valvular heart disease. DCM is one of the leading causes of mortality in patients with diabetes. However, the underlying pathogenesis of DCM has not been fully elucidated. Recent studies have revealed that non-coding RNAs (ncRNAs) in small extracellular vesicles (sEVs) are closely associated with DCM and may act as potential diagnostic and therapeutic targets. Here, we introduced the role of sEV-ncRNAs in DCM, summarized the current therapeutic advancements and limitations of sEV-related ncRNAs against DCM, and discussed their potential improvement.

The recurring outbreaks caused by emerging RNA viruses have fostered an increased interest in the research of the mechanisms that regulate viral life cycles and the pathological outcomes associated with infections. Although interactions at the protein level are well-studied, interactions mediated by RNA molecules are less explored. RNA viruses can encode small non-coding RNAs molecules (sncRNAs), including viral miRNAs (v-miRNAs), that play important roles in modulating host immune responses and viral replication by targeting viral or host transcripts. Starting from the analysis of public databases compiling the known repertoire of viral ncRNA molecules and the evolution of publications and research interests on this topic in the wake of the COVID-19 pandemic, we provide an updated view on the current knowledge on viral sncRNAs, with a focus on v-miRNAs encoded by RNA viruses, and their mechanisms of action. We also discuss the potential of these molecules as diagnostic and prognostic biomarkers for viral infections and the development of antiviral therapies targeting v-miRNAs. This review emphasizes the importance of continued research efforts to characterize sncRNAs encoded by RNA viruses, identifies the most relevant pitfalls in the study of these molecules, and highlights the paradigm changes that have occurred in the last few years regarding their biogenesis, prevalence and functional relevance in the context of host-pathogen interactions.

In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies.

The Colorado potato beetle (Leptinotarsa decemlineata (Say)) can cause extensive damage to agricultural crops worldwide and is a significant insect pest. This insect is notorious for its ability to evade various strategies deployed to control its spread and is known for its relative ease in developing resistance against different insecticides. Various molecular levers are leveraged by L. decemlineata for this resistance to occur, and a complete picture of the genes involved in this process is lacking. While small non-coding RNAs, including miRNAs, are differentially expressed in insects exposed to insecticides, levels of transcript coding for proteins underlying their synthesis remain to be characterized fully. The overarching objective of this work aims to fill that gap by assessing the expression of such targets in L. decemlineata exposed to cyantraniliprole and thiamethoxam. The expression status of Ago1, Ago2, Ago3, Dcr2a, Dcr2b, Expo-5, Siwi-1 and Siwi-2 transcripts were quantified via qRT-PCR in adult L. decemlineata treated with low and high doses of these compounds for different lengths of time. Variation in Ago1 and Dcr2b expression was notably observed in L. decemlineata exposed to cyantraniliprole, while thiamethoxam exposure was associated with the modulation of Dcr2a and Siwi-1 transcript levels. The down-regulation of Ago1 expression in L. decemlineata using dsRNA, followed by cyantraniliprole treatment, was associated with a reduction in the survival of insects with reduced Ago1 transcript expression. Overall, this work presents the insecticide-mediated modulation of transcripts associated with small non-coding RNA processing and showcases Ago1 as a target to further investigate its relevance in cyantraniliprole response.

Nephrolithiasis is a major public health concern associated with high morbidity and recurrence. Despite decades of research, the pathogenesis of nephrolithiasis remains incompletely understood, and effective prevention is lacking. An increasing body of evidence suggests that non-coding RNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a role in stone formation and stone-related kidney injury. MiRNAs have been studied quite extensively in nephrolithiasis, and a plethora of specific miRNAs have been implicated in the pathogenesis of nephrolithiasis, involving remarkable changes in calcium metabolism, oxalate metabolism, oxidative stress, cell–crystal adhesion, cellular autophagy, apoptosis, and macrophage (Mp) polarization and metabolism. Emerging evidence suggests a potential for miRNAs as novel diagnostic biomarkers of nephrolithiasis. LncRNAs act as competing endogenous RNAs (ceRNAs) to bind miRNAs, thereby modulating mRNA expression to participate in the regulation of physiological mechanisms in kidney stones. Small interfering RNAs (siRNAs) may provide a novel approach to kidney stone prevention and treatment by treating related metabolic conditions that cause kidney stones. Further investigation into these non-coding RNAs will generate novel insights into the mechanisms of renal stone formation and stone-related renal injury and might lead to new strategies for diagnosing and treating this disease.

Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a “Maestro” role in orchestrating several oncological and non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although a significant amount of work has been conducted on the role of nitric oxide (NO) and carbon monoxide (CO) and their inter-relationship in the field of oncology, research about hydrogen sulfide (H2S) remains in its infancy. Recently, non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H2S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H2S biosynthesis in different mammalian cells during the development and progression of human diseases; therefore, their targeting can be of great therapeutic benefit. In the current review, the authors shed the light onto the biosynthetic pathways of H2S and their regulation by miRNAs and lncRNAs in various oncological and non-oncological disorders.

Gene mutations that truncate the encoded protein can trigger the expression of related genes. The discovery of this compensatory response alters our thinking about genetic studies in humans and model organisms.

Intron sequences are removed from newly synthesized RNA and usually rapidly degraded. However, it now seems that introns have a surprising role — helping yeast cells survive when nutrients are scarce.

Abstract Lung cancer is the second cancer and the leading cause of tumor-related mortality worldwide. Angiogenesis is a crucial hallmark of cancer development and a promising target in lung cancer. However, the anti-angiogenic drugs currently used in the clinic do not achieve long-term efficacy and are accompanied by severe adverse reactions. Therefore, the development of novel anti-angiogenic therapeutic approaches for lung cancer is urgently needed. Non-coding RNAs (ncRNAs) participate in multiple biological processes in cancers, including tumor angiogenesis. Many studies have demonstrated that ncRNAs play crucial roles in tumor angiogenesis. This review discusses the regulatory functions of different ncRNAs in lung cancer angiogenesis, focusing on the downstream targets and signaling pathways regulated by these ncRNAs. Additionally, given the recent trend towards utilizing ncRNAs as cancer therapeutics, we also discuss the tremendous potential applications of ncRNAs as biomarkers or novel anti-angiogenic tools in lung cancer.

Abstract Circular RNAs (circRNAs) have become a research hotspot in recent years with their universality, diversity, stability, conservativeness, and spatiotemporal specificity. N6-methyladenosine (m6A), the most abundant modification in the eukaryotic cells, is engaged in the pathophysiological processes of various diseases. An increasing amount of evidence has suggested that m6A modification is common in circRNAs and is associated with their biological functions. This review summarizes the effects of m6A modification on circRNAs and their regulation mechanisms in cancers, providing some suggestions of m6A-modified circRNAs in cancer therapy.

Abstract As one of the leading causes of death, hematologic malignancies are associated with an ever-increasing incidence, and drug resistance and relapse of patients after treatment represent clinical challenges. Therefore, there are pressing demands to uncover biomarkers to indicate the development, progression, and therapeutic targets for hematologic malignancies. Circular RNAs (circRNAs) are covalently closed circular-single-stranded RNAs whose biosynthesis is regulated by various factors and is widely-expressed and evolutionarily conserved in many organisms and expressed in a tissue−/cell-specific manner. Recent reports have indicated that circRNAs plays an essential role in the progression of hematological malignancies. However, circRNAs are difficult to detect with low abundance using conventional techniques. We need to learn more information about their features to develop new detection methods. Herein, we sought to retrospect the current knowledge about the characteristics of circRNAs and summarized research on circRNAs in hematological malignancies to explore a potential direction.

Long non-coding RNAs (lncRNAs) act as important biological regulators in human cancers. The purpose of this study was to identify promising biomarkers for improved diagnosis and prognosis of papillary thyroid cancer (PTC). We analyzed the lncRNA expression profile of PTC patients and identified five upregulated and three downregulated lncRNAs as diagnostic biomarkers for PTC in our cohorts, which were confirmed using The Cancer Genome Atlas (TCGA) data. Several lncRNAs have been linked with lymph node (LN) metastasis in patients with PTC. A nomogram combining two lncRNAs, lnc-MPEG1-1:1 and lnc-ABCA12-5:2, with age, T stage, histological type, and predicted LN metastasis was developed. The area under the curve of the developed nomogram was 0.77 (0.73–0.81) in the TCGA training cohort and 0.88 (0.79–0.96) in our validation cohort. In particular, in vivo and in vitro experiments showed that overexpression of lnc-MPEG1-1:1 in PTC cell lines promoted the proliferation and migration of PTC. lnc-MPEG1-1:1 is overexpressed in the cytoplasm of PTC cells and functionally promotes cellular proliferation and migration and functions as a competitive endogenous RNA (ceRNA) by competitively occupying the shared binding sequences of miR-766-5p. lnc-MPEG1-1:1 knockdown suppressed epithelial-mesenchymal transition by miR-766-5p in PTC cells. Collectively, these results revealed a lnc-MPEG1-1:1/miR-766-5p pathway for thyroid cancer progression and suggest that a nomogram effectively predicted the LN metastasis in PTC.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. TNBC progression is sustained by recruitment of a strong tumor microenvironment (TME) mainly composed of cancer-associated fibroblasts (CAFs) able to endorse tumor hallmarks. Increasing evidences demonstrate that exosomes mediate the crosstalk between cancer cells and the TME. We examined TNBC-derived exosomes and their microRNA (miRNA) cargo in activation of normal fibroblasts (NFs) toward CAFs. We demonstrated that TNBC cell-derived exosomes increased NF collagen contraction and migration alongside CAF molecular markers. Exosome-activated fibroblasts promoted the invasion potential of normal breast epithelial cells, as assessed by an organotypic co-culture assay that resembled the in vivo context. We also investigated TNBC cell-derived exosome cargo in activating NFs to CAFs by performing small RNA sequencing. We found that the synergistic action of miR-185-5p, miR-652-5p, and miR-1246 boosted fibroblast migration and contraction, promoting specific CAF subspecialization toward a pro-migratory functional state. These data highlight the role of breast cancer cells in re-education of the TME and their contribution to tumor evolution.

Retinal gene therapy using RNA interference (RNAi) to silence targeted genes requires both efficacy and safety. Short hairpin RNAs (shRNAs) are useful for RNAi, but high expression levels and activity from the co-delivered passenger strand may cause undesirable cellular responses. Ago2-dependent shRNAs (agshRNAs) produce no passenger strand activity. To enhance efficacy and to investigate improvements in safety, we have generated VEGFA-targeting agshRNAs and microRNA (miRNA)-embedded agshRNAs (miR-agshRNAs) and inserted these RNAi effectors in Pol II/III-driven expression cassettes and lentiviral vectors (LVs). Compared with corresponding shRNAs, agshRNAs and miR-agshRNAs increased specificity and safety, while retaining a high knockdown efficacy and abolishing passenger strand activity. The agshRNAs also caused significantly smaller reductions in cell viability and reduced competition with the processing of endogenous miR21 compared with their shRNA counterparts. RNA sequencing (RNA-seq) analysis of LV-transduced ARPE19 cells revealed that expression of shRNAs in general leads to more changes in gene expression levels compared with their agshRNA counterparts and activation of immune-related pathways. In mice, subretinal delivery of LVs encoding tissue-specific miR-agshRNAs resulted in retinal pigment epithelium (RPE)-restricted expression and significant knockdown of Vegfa in transduced RPE cells. Collectively, our data suggest that agshRNAs and miR-agshRNA possess important advantages over shRNAs, thereby posing a clinically relevant approach with respect to efficacy, specificity, and safety.

Myocardial infarction is one of the leading diseases causing death and disability worldwide, and the revascularization of damaged tissues is essential for myocardial-injury repair. Circular RNAs (circRNAs) are widely involved in physiological and pathological processes in various systems throughout the body, and the role of circRNAs in cardiovascular disease is gaining attention. In this study, we determined that circERBB2IP is highly expressed in the hearts of newborn mice. Silencing or overexpression of circERBB2IP inhibited and promoted angiogenesis in vivo and in vitro, respectively. Mechanistically, the transcription factor GATA4 promotes the production of circERBB2IP. Furthermore, circERBB2IP functioned as an endogenous miR-145a-5p sponge and was able to sequester and repress miR-145a-5p activity, which led to an increased expression level of Smad5. In summary, circERBB2IP can promote angiogenesis after myocardial infarction through the miR-145a-5p/Smad5 axis. These data suggest that circERBB2IP may be a potential therapeutic target for the treatment of myocardial infarction.

Doxorubicin is a chemotherapeutic medication commonly used to treat many types of cancers, but it has side effects including vomiting, rash, hair loss, and bone marrow suppression. The most dangerous side effects are cardiomyopathy, cardiofibrosis, and heart failure, as doxorubicin generates cytotoxicity and stops DNA replication. There is no treatment to block these side effects. We have developed a transgenic mouse line overexpressing the circular RNA circNlgn and shown that circNlgn is a mediator of doxorubicin-induced cardiofibrosis. Increased expression of circNlgn decreased cardiac function and induced cardiofibrosis by upregulating Gadd45b, Sema4C, and RAD50 and activating p38 and pJNK in circNlgn transgenic heart. Silencing circNlgn decreased the effects of doxorubicin on cardiac cell activities and prevented doxorubicin-induced expression of fibrosis-associated molecules. The protein (Nlgn173) translated by circNlgn could bind and activate H2AX, producing γH2AX, resulting in upregulation of IL-1b, IL-2Rb, IL-6, EGR1, and EGR3. We showed that silencing these molecules in the signaling pathway prevented doxorubicin-induced cardiomyocyte apoptosis, increased cardiomyocyte viability, decreased cardiac fibroblast proliferation, and inhibited collagen production. This mechanism may hold therapeutic implications for mitigating the side effects of doxorubicin therapy in cancer patients.

Endothelial cell (EC) activity is essential for tissue regeneration in several (patho)physiological contexts. However, our capacity to deliver in vivo biomolecules capable of controlling EC fate is relatively limited. Here, we screened a library of microRNA (miR) mimics and identified 25 miRs capable of enhancing the survival of ECs exposed to ischemia-mimicking conditions. In vitro, we showed that miR-425-5p, one of the hits, was able to enhance EC survival and migration. In vivo, using a mouse Matrigel plug assay, we showed that ECs transfected with miR-425-5p displayed enhanced survival compared with scramble-transfected ECs. Mechanistically, we showed that miR-425-5p modulated the PTEN/PI3K/AKT pathway and inhibition of miR-425-5p target genes (DACH1, PTEN, RGS5, and VASH1) phenocopied the pro-survival. For the in vivo delivery of miR-425-5p, we modulated small extracellular vesicles (sEVs) with miR-425-5p and showed, in vitro, that miR-425-5p-modulated sEVs were (1) capable of enhancing the survival of ECs exposed to ischemia-mimic conditions, and (2) efficiently internalized by skin cells. Finally, using a streptozotocin-induced diabetic wound healing mouse model, we showed that, compared with miR-scrambled-modulated sEVs, topical administration of miR-425-5p-modulated sEVs significantly enhanced wound healing, a process mediated by enhanced vascularization and skin re-epithelialization.

Extracellular vesicles (EVs) are membrane-encapsulated vesicles released by almost all cell types, which participate in intercellular communication by delivering different types of molecular cargoes, such as non-coding RNAs (ncRNAs). Accumulating evidence suggests that tumor-derived EVs act as a bridge for intercellular crosstalk between tumor cells and surrounding cells, including immune cells. Tumor-derived EVs containing ncRNAs (TEV-ncRNAs) mediate intercellular crosstalk to manipulate immune responses and affect the malignant phenotypes of cancer cells. In this review, we summarize the double-edged roles and the underlying mechanisms of TEV-ncRNAs in regulating innate and adaptive immune cells. We also highlight the advantages of using TEV-ncRNAs in liquid biopsies for cancer diagnosis and prognosis. Moreover, we outline the use of engineered EVs to deliver ncRNAs and other therapeutic agents for cancer therapy.

Abstract Background Colitis‐associated cancer (CAC) is one of the most severe complications of inflammatory bowel disease (IBD), which has caused a worse survival rate in IBD patients. Although the exact aetiology and pathogenesis of CAC are not completely elucidated, evidence indicates that non‐coding RNAs are closely involved and play a key role. Methods This review aims to summarise the major findings of non‐coding RNAs in the development of CAC and present the potential mechanistic links between non‐coding RNAs and CAC pathogenesis. The results show that non‐coding RNAs can hinder DNA mismatch repair proteins and obstruct chromosome passenger complexes to increase microsatellite instability and accumulate chromosomal instability, respectively. The data also suggest that DNA promoter methylation or RNA methylation modifications of non‐coding RNA are the main mechanisms to regulate oncogene or tumour suppressor expression during the CAC progression. Other factors, including gut microbiota perturbations, immune dysregulation and barrier dysfunction, are also regulated and influenced by non‐coding RNAs. Besides, non‐coding RNAs as molecular managers are associated with multiple critical signalling pathways governing the initiation, progression and metastasis of CAC, including the janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor‐kappa B (NF‐κB), extracellular signal‐regulated kinase (ERK), Toll‐like receptor 4 (TLR4), Wnt/β‐catenin and phosphatidylinositol 3‐Kinase/Protein Kinase B (PI3K/AKT) pathways. In addition, non‐coding RNAs can be detected in colon tissues or blood, and their aberrant expressions and diagnostic and prognostic roles are also discussed and confirmed in CAC patients. Conclusions It is believed that a deepening understanding of non‐coding RNAs in CAC pathogenesis may prevent the progression to carcinogenesis, and will offer new effective therapies for CAC patients.

Prostate cancer (PCa), bladder cancer (BC), and renal cell cancer (RCC) are the most common urologic tumours in males. N6-methyladenosine (m6A), adenosine N6 methylation, is the most prevalent RNA modification in mammals. Increasing evidence suggests that m6A plays a crucial role in cancer development. In this review, we comprehensively analyzed the influence of m6A methylation on Prostate cancer, bladder cancer, and renal cell cancer and the relationship between the expression of relevant regulatory factors and their development and occurrence, which provides new insights and approaches for the early clinical diagnosis and targeted therapy of urologic malignancies.

Oxidative stress is a state in which oxidants are produced in excess in the body’s tissues and cells, resulting in a biological imbalance amid the generation of reactive oxygen and nitrogen species (RONS) from redox reactions. In case of insufficient antioxidants to balance, the immune system triggers signaling cascades to mount inflammatory responses. Oxidative stress can have deleterious effects on major macromolecules such as lipids, proteins, and nucleic acids, hence, Oxidative stress and inflammation are among the multiple factors contributing to the etiology of several disorders such as diabetes, cancers, and cardiovascular diseases. Non-coding RNAs (ncRNAs) which were once referred to as dark matter have been found to function as key regulators of gene expression through different mechanisms. They have dynamic roles in the onset and development of inflammatory and oxidative stress-related diseases, therefore, are potential targets for the control of those diseases. One way of controlling those diseases is through the use of natural products, a rich source of antioxidants that have drawn attention with several studies showing their involvement in combating chronic diseases given their enormous gains, low side effects, and toxicity. In this review, we highlighted the natural products that have been reported to target ncRNAs as mediators of their biological effects on oxidative stress and several inflammation-associated disorders. Those natural products include Baicalein, Tanshinone IIA, Geniposide, Carvacrol/Thymol, Triptolide, Oleacein, Curcumin, Resveratrol, Solarmargine, Allicin, aqueous extract or pulp of Açai, Quercetin, and Genistein. We also draw attention to some other compounds including Zanthoxylum bungeanum, Canna genus rhizome, Fuzi-ganjiang herb pair, Aronia melanocarpa, Peppermint, and Gingerol that are effective against oxidative stress and inflammation-related disorders, however, have no known effect on ncRNAs. Lastly, we touched on the many ncRNAs that were found to play a role in oxidative stress and inflammation-related disorders but have not yet been investigated as targets of a natural product. Shedding more light into these two last points of shadow will be of great interest in the valorization of natural compounds in the control and therapy of oxidative stress- and inflammation-associated disorders.

Colorectal cancer (CRC) is a dangerous form of cancer that affects the gastrointestinal tract. It is a major global health concern, and the aggressive behavior of tumor cells makes it difficult to treat, leading to poor survival rates for patients. One major challenge in treating CRC is the metastasis, or spread, of the cancer, which is a major cause of death. In order to improve the prognosis for patients with CRC, it is necessary to focus on ways to inhibit the cancer's ability to invade and spread. Epithelial-mesenchymal transition (EMT) is a process that is linked to the spread of cancer cells, also known as metastasis. The process transforms epithelial cells into mesenchymal ones, increasing their mobility and ability to invade other tissues. This has been shown to be a key mechanism in the progression of colorectal cancer (CRC), a particularly aggressive form of gastrointestinal cancer. The activation of EMT leads to increases in the spread of CRC cells, and during this process, levels of the protein E-cadherin decrease while levels of N-cadherin and vimentin increase. EMT also contributes to the development of resistance to chemotherapy and radiation therapy in CRC. Non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a role in regulating EMT in CRC, often through their ability to ''sponge'' microRNAs. Anti-cancer agents have been shown to suppress EMT and reduce the progression and spread of CRC cells. These findings suggest that targeting EMT or related mechanisms may be a promising approach for treating CRC patients in the clinic.

Up to 18% of cancer-related deaths worldwide are attributed to lung tumor and global burden of this type of cancer is ascending. Different factors are responsible for development of lung cancer such as smoking, environmental factors and genetic mutations. EZH2 is a vital protein with catalytic activity and belongs to PCR2 family. EZH2 has been implicated in regulating gene expression by binding to promoter of targets. The importance of EZH2 in lung cancer is discussed in current manuscript. Activation of EZH2 significantly elevates the proliferation rate of lung cancer. Furthermore, metastasis and associated molecular mechanisms including EMT undergo activation by EZH2 in enhancing the lung cancer progression. The response of lung cancer to therapy can be significantly diminished due to EZH2 upregulation. Since EZH2 increases tumor progression, anti-cancer agents suppressing its expression reduce malignancy. In spite of significant effort in understanding modulatory function of EZH2 on other pathways, it appears that EZH2 can be also regulated and controlled by other factors that are described in current review. Therefore, translating current findings to clinic can improve treatment and management of lung cancer patients.

Autophagy is defined as a “self-digestion” signal, and it is a cell death mechanism its primary function is degrading toxic agents and aged organelles to ensure homeostasis in cells. The basic leve ls of autophagy are found in cells, and when its levels exceed to standard threshold, cell death induction is observed. Autophagy dysregulation in cancer has been well-documented, and regulation of this pathway by epigenetic factors, especially microRNAs (miRNAs), is interesting and noteworthy. miRNAs are considered short endogenous RNAs that do not encode functional proteins, and they are essential regulators of cell death pathways such as apoptosis, necroptosis, and autophagy. Accumulating data has revealed miRNA dysregulation (upregulation or downregulation) during tumor progression, and their therapeutic manipulation provides new insight into cancer therapy. miRNA/autophagy axis in human cancers has been investigated an exciting point is the dual function of both autophagy and miRNAs as oncogenic and onco-suppressor factors. The stimulation of pro-survival autophagy by miRNAs can increase the survival rate of tumor cells and mediates cancer metastasis via EMT inductionFurthermore, pro-death autophagy induction by miRNAs has a negative impact on the viability of tumor cells and decreases their survival rate. The miRNA/autophagy axis functions beyond regulating the growth and invasion of tumor cells, and they can also affect drug resistance and radio-resistance. These subjects are covered in the current review regarding the new updates provided by recent experiments.