Search Results (2,613)

Chronic obstructive pulmonary disease (COPD) and lung cancer represent formidable challenges in global health, characterized by intricate pathophysiological mechanisms and multifaceted disease progression. This comprehensive review integrates insights from diverse perspectives to elucidate the intricate roles of long non-coding RNAs (lncRNAs) in the pathogenesis of COPD and lung cancer, focusing on their diagnostic, prognostic, and therapeutic implications. In the context of COPD, dysregulated lncRNAs, such as NEAT1, TUG1, MALAT1, HOTAIR, and GAS5, emerge as pivotal regulators of genes involved in the disease pathogenesis and progression. Their identification, profiling, and correlation with the disease severity present promising avenues for prognostic and diagnostic applications, thereby shaping personalized disease interventions. These lncRNAs are also implicated in lung cancer, underscoring their multifaceted roles and therapeutic potential across both diseases. In the domain of lung cancer, lncRNAs play intricate modulatory roles in disease progression, offering avenues for innovative therapeutic approaches and prognostic indicators. LncRNA-mediated immune responses have been shown to drive lung cancer progression by modulating the tumor microenvironment, influencing immune cell infiltration, and altering cytokine production. Their dysregulation significantly contributes to tumor growth, metastasis, and chemo-resistance, thereby emphasizing their significance as therapeutic targets and prognostic markers. This review summarizes the transformative potential of lncRNA-based diagnostics and therapeutics for COPD and lung cancer, offering valuable insights into future research directions for clinical translation and therapeutic development. Full article

A growing body of evidence indicates that the G protein-coupled bile acid receptor, TGR5, plays a critical role in multiple physiological processes ranging from metabolic disorders to cancers. However, the biological functions of TGR5 in cervical cancer (CC) have not been elucidated. Here, using TGR5 knockout mice, we found that a deficiency of TGR5 leads to greater sensitivity to the progression of cervical inflammation. Activation of TGR5 by its specific ligands significantly attenuated the malignant behavior of CC cells. In addition, we found that TGR5 can negatively modulate the expression of lncRNA HCP5 by blocking its transcription activation when mediated by p65. HCP5 was highly expressed in CC tissues, which was positively correlated with the poor prognosis of CC patients. HCP5 knockdown notably restrained CC cell proliferation, colony formation, and migration in vitro, and inhibited tumor growth in vivo. Furthermore, HCP5 can function as the molecular sponge for miR-139-5p to upregulate DNA damage-induced transcript 4 (DDIT4) in CC cells. Murine xenograft studies demonstrated that TGR5 suppressed the tumor formation of CC cells and downregulated HCP5 and DDIT4 while increasing miR-139-5p in the xenografts. Taken together, these findings, for the first time, indicate that TGR5 inhibits CC progression by regulating the HCP5/miR-139-5p/DDIT4 axis, suggesting that it may represent a novel and potent target for CC treatment. Full article

This study investigates novel short-lived long noncoding RNAs (lncRNAs) in mice with altered expression in metabolic dysfunction-associated steatotic liver (MASH) and liver fibrosis. LncRNAs share similarities with mRNAs in their transcription by RNA polymerase II, possession of a 5′ cap structure, and presence of a polyA tail. We identified two lncRNAs, Kcnq1ot1 and Rmst, significantly decreased in both conditions. These lncRNAs showed dramatic expression changes in MASH livers induced by Western diets and CCl₄, and in fibrotic livers induced by CCl₄ alone. The decrease was more pronounced in liver fibrosis, suggesting their potential as biomarkers for disease progression. Our findings are consistent across different fibrosis models, indicating a crucial role for these lncRNAs in MASH and liver fibrosis in mice. With MASH becoming a global health issue and its progression to fibrosis associated with hepatocarcinogenesis and poor prognosis, understanding the underlying mechanisms is critical. This research contributes to elucidating lncRNA functions in murine liver diseases and provides a foundation for developing novel therapeutic strategies targeting lncRNAs in MASH and liver fibrosis, offering new avenues for potential therapeutic interventions. Full article

Neurodegeneration occurs naturally as humans age, but the presence of additional pathogenic mechanisms yields harmful and consequential effects on the brain. Alzheimer’s disease (AD), the most common form of dementia, is a composite of such factors. Despite extensive research to identify the exact causes of AD, therapeutic approaches for treating the disease continue to be ineffective, indicating important gaps in our understanding of disease mechanisms. Long non-coding RNAs (lncRNAs) are an endogenous class of regulatory RNA transcripts longer than 200 nucleotides, involved in various regulatory networks, whose dysregulation is evident in several neural and extraneural diseases. LncRNAs are ubiquitously expressed across all tissues with a wide range of functions, including controlling cell differentiation and development, responding to environmental stimuli, and other physiological processes. Several lncRNAs have been identified as potential contributors in worsening neurodegeneration due to altered regulation during abnormal pathological conditions. Within neurological disease, lncRNAs are prime candidates for use as biomarkers and pharmacological targets. Gender-associated lncRNA expression is altered in a gender-dependent manner for AD, suggesting more research needs to be focused on this relationship. Overall, research on lncRNAs and their connection to neurodegenerative disease is growing exponentially, as commercial enterprises are already designing and employing RNA therapeutics. In this review we offer a comprehensive overview of the current state of knowledge on the role of lncRNAs in AD and discuss the potential implications of lncRNA as potential therapeutic targets and diagnostic biomarkers in patients with Alzheimer’s disease. Full article

Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process in the progression and metastasis of melanoma. Recent research has highlighted the significant role of epigenetic modifications in regulating angiogenesis. This review comprehensively examines the current understanding of how epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, influence angiogenic pathways in melanoma. DNA methylation, a key epigenetic modification, can silence angiogenesis inhibitors such as thrombospondin-1 and TIMP3 while promoting pro-angiogenic factors like vascular endothelial growth factor (VEGF). Histone modifications, including methylation and acetylation, also play a pivotal role in regulating the expression of angiogenesis-related genes. For instance, the acetylation of histones H3 and H4 is associated with the upregulation of pro-angiogenic genes, whereas histone methylation patterns can either enhance or repress angiogenic signals, depending on the specific histone mark and context. Non-coding RNAs, particularly microRNAs (miRNAs) further modulate angiogenesis. miRNAs, such as miR-210, have been identified as key regulators, with miR-9 promoting angiogenesis by targeting E-cadherin and enhancing the expression of VEGF. This review also discusses the therapeutic potential of targeting epigenetic modifications to inhibit angiogenesis in melanoma. Epigenetic drugs, such as DNA methyltransferase inhibitors (e.g., 5-azacytidine) and histone deacetylase inhibitors (e.g., Vorinostat), have shown promise in preclinical models by reactivating angiogenesis inhibitors and downregulating pro-angiogenic factors. Moreover, the modulation of miRNAs and lncRNAs presents a novel approach for anti-angiogenic therapy. Full article

The meat production traits of pigs are influenced by the expression regulation of multiple gene types, including mRNAs, miRNAs, and lncRNAs. To study the differences in meat production traits at the transcriptional level among individuals with different growth rates, the longissimus dorsi samples from eight Duroc × Bama Xiang F2 crossbred pigs with a fast growth rate (high gTroup) or a slow growth rate (low group) were selected to perform whole transcriptome sequencing and ceRNA regulatory network construction. This study first analyzed the differences in physiological and biochemical indicators, muscle histological characteristics, and muscle fiber types. A total of 248 mRNAs, 25 miRNAs, and 432 lncRNAs were identified as differentially expressed by whole transcriptome sequencing. Key genes that may influence meat production traits include MTMR14, PPP1R3A, PYGM, PGAM2, MYH1, and MYH7. The ceRNA regulatory network map showed that ENSSSCG00000042061-ssc-mir-208b-MYH7, ENSSSCG00000042223-ssc-mir-146a-MTMR14, ENSSSCG00000045539-ssc-mir-9-3-MYH1, and ENSSSCG00000047852-ssc-mir-103-1-PPP1R3A may be the key factors affecting meat production traits through their regulatory relationships. This study provides valuable insights into the molecular mechanisms underlying porcine muscle development and can aid in improving meat production traits. Full article

Light is one of the most important factors regulating plant gene expression patterns, metabolism, physiology, growth, and development. To explore how light may induce or alter transcript splicing, we conducted RNA-Seq-based transcriptome analyses by comparing the samples harvested as etiolated seedlings grown under continuous dark conditions vs. the light-treated green seedlings. The study aims to reveal differentially regulated protein-coding genes and novel long noncoding RNAs (lncRNAs), their light-induced alternative splicing, and their association with biological pathways. We identified 14,766 differentially expressed genes, of which 4369 genes showed alternative splicing. We observed that genes mapped to the plastid-localized methyl-erythritol-phosphate (MEP) pathway were light-upregulated compared to the cytosolic mevalonate (MVA) pathway genes. Many of these genes also undergo splicing. These pathways provide crucial metabolite precursors for the biosynthesis of secondary metabolic compounds needed for chloroplast biogenesis, the establishment of a successful photosynthetic apparatus, and photomorphogenesis. In the chromosome-wide survey of the light-induced transcriptome, we observed intron retention as the most predominant splicing event. In addition, we identified 1709 novel lncRNA transcripts in our transcriptome data. This study provides insights on light-regulated gene expression and alternative splicing in rice. Full article

Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in sFGR using molecular biology experiments and gain- or loss-of-function assays. We found that the levels of MALAT1, ERRγ, and HSD17B1 were downregulated and that of miR-424 was upregulated in the placental shares of the smaller twins. Moreover, angiogenesis was impaired in the placental share of the smaller fetus and MALAT1 could regulate the paracrine effects of trophoblasts on endothelium angiogenesis and proliferation by regulating miR-424. In trophoblasts, MALAT1 could competitively bind to miR-424 to regulate the expression of ERRγ and HSD17B1, thus regulating trophoblast invasion and migration. MALAT1 overexpression could decrease apoptosis and promote proliferation, alleviating cell damage induced by hypoxia. Taken together, the downregulation of MALAT1 can reduce the expression of ERRγ and HSD17B1 by competitively binding to miR-424, impairing the proangiogenic effect of trophoblasts, trophoblast invasion and migration, and the ability of trophoblasts to compensate for hypoxia, which may be involved in the pathogenesis of sFGR through various aspects. Full article

The lion-head goose is the only large goose species in China, and it is one of the largest goose species in the world. Lion-head geese have a strong tolerance for massive energy intake and show a priority of fat accumulation in liver tissue through special feeding. Therefore, the aim of this study was to investigate the impact of high feed intake compared to normal feeding conditions on the transcriptome changes associated with fatty liver development in lion-head geese. In this study, 20 healthy adult lion-head geese were randomly assigned to a control group (CONTROL, n = 10) and high-intake-fed group (CASE, n = 10). After 38 d of treatment, all geese were sacrificed, and liver samples were collected. Three geese were randomly selected from the CONTROL and CASE groups, respectively, to perform whole-transcriptome analysis to analyze the key regulatory genes. We identified 716 differentially expressed mRNAs, 145 differentially expressed circRNAs, and 39 differentially expressed lncRNAs, including upregulated and downregulated genes. GO enrichment analysis showed that these genes were significantly enriched in molecular function. The node degree analysis and centrality metrics of the mRNA–lncRNA–circRNA triple regulatory network indicate the presence of crucial functional nodes in the network. We identified differentially expressed genes, including HSPB9, Pgk1, Hsp70, ME2, malic enzyme, HSP90, FADS1, transferrin, FABP, PKM2, Serpin2, and PKS, and we additionally confirmed the accuracy of sequencing at the RNA level. In this study, we studied for the first time the important differential genes that regulate fatty liver in high-intake feeding of the lion-head goose. In summary, these differentially expressed genes may play important roles in fatty liver development in the lion-head goose, and the functions and mechanisms should be investigated in future studies. Full article

microRNA-204-5p (miR-204) is a small noncoding RNA with diverse regulatory roles in breast cancer (BC) development and progression. miR-204 is implicated in the instauration of fundamental traits acquired during the multistep development of BC, known as the hallmarks of cancer. It may act as a potent tumor suppressor by inhibiting key cellular processes like angiogenesis, vasculogenic mimicry, invasion, migration, and metastasis. It achieves this by targeting multiple master genes involved in these processes, including HIF-1α, β-catenin, VEGFA, TGFBR2, FAK, FOXA1, among others. Additionally, miR-204 modulates signaling pathways like PI3K/AKT and interacts with HOTAIR and DSCAM-AS1 lncRNAs, further influencing tumor progression. Beyond its direct effects on tumor cells, miR-204 shapes the tumor microenvironment by regulating immune cell infiltration, suppressing pro-tumorigenic cytokine production, and potentially influencing immunotherapy response. Moreover, miR-204 plays a crucial role in metabolic reprogramming by directly suppressing metabolic genes within tumor cells, indirectly affecting metabolism through exosome signaling, and remodeling metabolic flux within the tumor microenvironment. This review aims to present an update on the current knowledge regarding the role of miR-204 in the hallmarks of BC. In conclusion, miR-204 is a potential therapeutic target and prognostic marker in BC, emphasizing the need for further research to fully elucidate its complex roles in orchestrating aggressive BC behavior. Full article

Pancreatic cancer is a prevalent malignant tumor with rising medication resistance and mortality. Due to a dearth of specific and trustworthy biomarkers and therapeutic targets, pancreatic cancer early detection and treatment are still not at their best. Exosomal LncRNAs have been found to be plentiful and persistent within exosomes, and they are capable of functioning whether the exosomes are traveling to close or distant cells. Furthermore, increasing evidence suggests that exosomal LncRNA, identified as an oncogene or tumor suppressor-control the growth, metastasis, and susceptibility of pancreatic cancer to chemotherapy and radiation therapy. Promising prospects for both antitumor targets and diagnostic biomarkers are exosomal LncRNAs. The primary features of exosomal LncRNAs, their biological roles in the onset and progression of pancreatic cancer, and their potential as therapeutic targets and diagnostic molecular markers are outlined in this review. Full article

Plant functional traits are an important indicator for the comprehensive evaluation of community stability and resilience. Therefore, exploring the variations and relationships among leaf functional traits at different maturity levels during forest restoration can deepen the understanding of plant adaptation strategies and community assembly. In this study, we measured the leaf area (LA), specific leaf area (SLA), photosynthetic pigments, non-structural carbohydrates (NSCs), leaf nitrogen content (LNC), and leaf phosphorus content (LPC) of dominant tree species in three communities with different maturity levels (defined by species composition, biodiversity and spatial structure) in a monsoon forest located in the northern margin of the tropics in China, and explored the variation and relationships among different leaf traits at individual, species, and community scales. The results showed that maturity levels significantly affected leaf functional traits. With the increase in maturity levels, SLA increased, and leaf SS and NSCs decreased, while other leaf functional traits did not show a consistent pattern. In different communities, NSCs, Chl (a:b), SS:St or Car had a trade-off or synergistic relationship with leaf economic spectrum. Additionally, the LPC, LNC, and starch were the key traits in response to selection pressure at maturity levels, inter-specific and intra-specific scales, respectively, and the trait–trait relationships were stronger or more extreme as the scale was narrowed. Therefore, when evaluating the development and succession of tropical monsoon forest communities, the selection of leaf functional characteristics and the determination of the research scale should be comprehensively and systematically considered. Full article

As a representative item of chemical carcinogen, MNNG is closely associated with the onset of gastric cancer (GC), where N6-methyladonosine (m6A) RNA methylation is recognized as a critical epigenetic event. In our previous study, we found that the m6A modification by methyltransferase METTL3 was up-regulated in MNNG-exposed malignant GES-1 cells (MC cells) compared to control cells in vitro, and long non-coding RNA SNHG7 as a downstream target of the METTL3. However, the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC remains unclear. In the present study, we continuously investigate the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC. RIP-PCR and m6A-IP-qPCR were used to examine the molecular mechanism underlying the METTL3/m6A/SNHG7 axis in MNNG-induced GC. A METTL3 knockout mice model was constructed and exposed by MNNG. Western blot analysis, IHC analysis, and RT-qPCR were used to measure the expression of METTL3, SNHG7, and EMT markers. In this study, we demonstrated that in MNNG-induced GC tumorigenesis, the m6A modification regulator METTL3 facilitates cellular EMT and biological functions through the m6A/SNHG7 axis using in vitro and in vivo models. In conclusion, our study provides novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment. Full article

Cardiac mesoderm enhancer-associated non-coding RNA (CARMN), an evolutionarily conserved long non-coding RNA (lncRNA), serves as the host gene for the miR143/145 cluster. It plays a crucial role in cardiovascular cell differentiation and the maintenance of vascular smooth muscle cell (VSMC) homeostasis, which are vital for normal physiological processes. Specifically, CARMN is associated with the pathological progression of cardiovascular diseases such as atherosclerosis, abdominal aortic aneurysm, and chronic heart failure. Moreover, it acts as a tumor suppressor in various cancers, including hepatocellular carcinoma, bladder cancer, and breast cancer, highlighting its potential as a beneficial biomarker and therapeutic target. This review provides a detailed examination of the roles of CARMN, its evolutionary conservation, expression patterns, and regulatory mechanisms. It also outlines its significant implications in the diagnosis, prognosis, and treatment of these diseases, underscoring the need for further translational research to exploit its clinical potential. Full article

Electronic cigarette (e-cig) use, otherwise known as “vaping”, is widespread among adolescent never-smokers and adult smokers seeking a less-harmful alternative to combustible tobacco products. To date, however, the long-term health consequences of vaping are largely unknown. Many toxicants and carcinogens present in e-cig vapor and tobacco smoke exert their biological effects through epigenetic changes that can cause dysregulation of disease-related genes. Long non-coding RNAs (lncRNAs) have emerged as prime regulators of gene expression in health and disease states. A large body of research has shown that lncRNAs regulate genes involved in the pathogenesis of smoking-associated diseases; however, the utility of lncRNAs for assessing the disease-causing potential of vaping remains to be fully determined. A limited but growing number of studies has shown that lncRNAs mediate dysregulation of disease-related genes in cells and tissues of vapers as well as cells treated in vitro with e-cig aerosol extract. This review article provides an overview of the evolution of e-cig technology, trends in use, and controversies on the safety, efficacy, and health risks or potential benefits of vaping relative to smoking. While highlighting the importance of lncRNAs in cell biology and disease, it summarizes the current and ongoing research on the modulatory effects of lncRNAs on gene regulation and disease pathogenesis in e-cig users and in vitro experimental settings. The gaps in knowledge are identified, priorities for future research are highlighted, and the importance of empirical data for tobacco products regulation and public health is underscored. Full article