Role Of Long Non-coding RNAs Research Articles

The mechanism study of LncRNA AC012181.2 targeting HERPUD1 protein in regulating stromal stem cells participating in metabolic reprogramming for gastric cancer metastasis.

To investigate the role of long non-coding RNAs (lncRNAs) in the metabolic reprogramming of gastric cancer through their regulation of mesenchymal stem cells (MSCs) and HERPUD1 protein targets, aiming to elucidate mechanisms that could lead to novel therapeutic strategies. The RNA-seq was performed on BGC and hMSC-BGC cells to perform LncRNA screening. And we employed cell culture techniques using hMSC-BM and BGC823 cells, treated with various genetic interventions including siRNA and overexpression vectors. Techniques such as cell viability assays, quantitative PCR (qPCR), Western blotting, RNA pull-down and RNA-FISH were utilized to validate the interaction between lncRNA AC012181.2 and HERPUD1 protein. Flow cytometry were utilized to analyze the impacts of lncRNA AC012181.2 on gene and protein expression related to cancer metabolism. Additionally, a tumorigenic model in nude mice was used to observe the in vivo effects. Modulation of AC012181.2 in MSCs significantly affected the proliferation, migration, and invasion capabilities of BGC823 gastric cancer cells. Knockdown of AC012181.2 resulted in reduced tumor growth in mouse models, along with changes in key gene and protein expression levels associated with cancer metabolism. Overexpression of AC012181.2 showed the opposite effect, enhancing tumor growth and altering cellular behaviors and molecular expressions in favor of cancer progression. The lncRNA AC012181.2 is crucial for gastric cancer metabolic reprogramming by regulating HERPUD1 Protein. Targeting it offers a promising avenue to impact the tumor microenvironment and develop novel gastric cancer therapies.

Hypoxic Secretome and Exosomes Derived From Human Glioblastoma Cells (U87MG) Promote Protumorigenic Phenotype of Microglia in Vitro.

Glioblastoma multiforme (GBM), a highly heterogeneous CNS tumor known for its highest incidence rates and poor prognosis has shown limited success in the therapies due to hypoxia-driving immune-suppression in the tumor microenvironment (TME). Emerging evidence highlights the involvement of tumor cell-derived exosomes in tumor-associated microglia polarization via transfer of exosomal onco-proteins and miRNAs. Although the regulatory role of long noncoding RNAs (lncRNAs) in immune signaling are known, its mechanism in microglial polarization via exosomes in GBM still remains poorly understood. In our study, we found that in comparison to the normoxic GBM-derived exosomes lncRNA H19 was significantly upregulated in hypoxic GBM-derived exosomes. Hypoxic GBM-derived exosomes and secretome (conditioned media) caused the reduction in the % phagocytosis of microglia as compared with the control group. Moreover, GBM secretome caused increase in the M2-specific genes (IL10, STAT-3, CD163, CD206) in microglia indicating its polarization to the protumorigenic (M2) phenotype. LncRNA H19 knocked down GBM-secretome treatment in microglia further reduced the STAT-3 expression indicating H19 mediated signaling. Overall, our results suggest the involvement of hypoxic exosomes and lncRNA H19 in microglial polarization and H19 as a potential target.

H19 promotes polarization and alternative splicing in tumor-associated macrophages, facilitating pancreatic cancer progression.

Tumor-associated macrophages (TAMs) play a crucial physiological role in the pancreatic tumor microenvironment. However, the role of long non-coding RNAs (lncRNAs) in TAMs within pancreatic tumors remains unclear. By lncRNA sequencing between TAMs and resident macrophages from normal tissues in pancreatic cancer, it is found that H19 is highly expressed in TAMs and is correlated with the prognosis and stages of pancreatic cancer. Constructing a co-culture model of THP-1 derived TAMs and pancreatic cancer cells, H19 promotes the polarization of TAMs towards the M2 phenotype and the secretion of IL-6, IL-10, and TGF-β, both in vivo and in vitro, indirectly enhancing pancreatic cancer proliferation and metastasis. Mechanistically, H19 competitively binds to the mRNA of YTHDC1 with MiR-107, and also interacts with the YTHDC1 protein, regulating the stability of SRSF1 and thereby affecting the alternative splicing of IL-6 and IL-10. Utilizing organoids and the patient-derived xenograft (PDX) model, it is found that ruxolitinib may represent a promising treatment option for PDAC patients with high H19 expression.

The Emerging Role of Long Non-Coding RNA 01296 in Human Malignancies.

Long non-coding RNAs (lncRNAs) refer to a group of RNA molecules that exceed a length of 200 nucleotides and lack the ability to code proteins. Numerous studies suggest that lncRNAs significantly contribute to the onset and progression of various forms of cancers. A specific lncRNA, known as long non-coding RNA 01296 (LINC01296), is extensively expressed in human malignancies. The level of LINC01296 has been shown to correlate with the progression and prognosis of cancers. Moreover, numerous scientific investigations have provided evidence that the dysregulation of LINC01296 functioning as a competitive endogenous RNA (ceRNA) exerts a profound influence on various aspects of cancer cell behavior, including proliferation, apoptosis, invasion, metastasis, and cell cycle progression, by means of regulating target genes and signaling pathways. An increasing body of data strongly suggests that LINC01296 may serve as a valuable biomarker for predicting cancer prognosis and could represent a promising therapeutic target for cancer intervention. In this comprehensive review, we summarize the recent advancements in our understanding of the role, underlying mechanisms, and clinical significance of LINC01296 in malignant tumors. The findings suggest that LINC01296 may be both a reliable biomarker and a potential therapeutic target for cancers.

The Role of Long Non-coding RNA (NKILA and LINC00993) as Tumour Biomarkers in Breast Cancer

Background: Long non-coding RNAs (NKILA and LINC00993) are downregulated in breast cancer (BC) and can have potential use as a novel tumor biomarker. The Aim of the work is to investigate the LncRNAs (NKILA and LINC00993) and cytokines (NF-κB and CXCL-1) as potential biomarkers in BC. Methods: This Cross-sectional study included sixty-four pairs of surgically resected human breast cancer tissues and adjacent breast tissues. Expressions of LncRNAs (NKILA, LINC00993) and (NF-κB, CXCL1) cytokines were detected using real-time quantitative polymerase chain reaction (qPCR) analysis, Results: There was a significant decrease in LncRNAs (NKILA, LINC00993) levels in tumor tissue compared to normal tissue (P<0.001). Also, there was a significant increase in NF-κB and CXCL1 levels in tumor tissue compared to normal tissue (P<0.001). ROC curve analysis indicated that the LncRNAs (NKILA, LINC00993) expression levels could be considered a promising marker for the diagnosis of breast cancer patients with a sensitivity (90.6%, 92.2% respectively). Also, cytokines (NF-κB and CXCL-1) expression levels could be considered a promising marker for the diagnosis of breast cancer patients with a sensitivity and specificity of 87.5%, and 89.1% respectively). Conclusion: These findings suggest that LncRNAs (NKILA, LINC00993) and cytokines (NF-κB and CXCL-1) can be used as novel biomarkers for breast cancer.

Elucidating role of long non-coding RNAs of Tamarindus indica Linn. in post-transcriptional gene regulation

Tamarindus indica Linn., commonly known as tamarind, is a rich source of carbohydrates, proteins, lipids, fatty acids, vitamins, minerals and bioactive compounds. It is well established that long non-coding RNAs (lncRNAs) plays an important role in transcriptional, post-transcriptional and epigenetic regulation. Despite the availability of tamarind genome information, a handful of studies have been done on its non-coding genome, especially lncRNAs. In this study, we have computationally predicted lncRNAs from the coding DNA sequences of T. indica and analysed the sequences. We experimentally validated seven randomly chosen lncRNAs by performing quantitative Real Time Polymerase Chain Reaction (qRT-PCR). 320 lncRNAs have been predicted and sequence analysis of these predicted, lncRNAs reveals the presence of different motifs and tandem repeats. Along with the experimental validation of 7 randomly chosen lncRNAs, functional analysis of the predicted lncRNAs and their targets elucidated their roles in various biological pathways. We believe prediction and validation of the lncRNAs along with their interaction with mRNAs will enhance our knowledge about the non-coding genome of tamarind and their involvement in post transcriptional gene regulation, medicinal properties, metabolic engineering, stress tolerance and genome editing.

The Role of Long Non-Coding RNA in the Pathogenesis of Psoriasis.

Psoriasis is a chronic immune-mediated disease with complex pathogenesis. The altered proliferation and differentiation of keratinocytes, together with the activity of dendritic cells and T cells, are crucial drivers of psoriasis progression. Long non-coding RNAs (lncRNAs) are composed of over 200 nucleotides and exert a large variety of functions, including the regulation of gene expression. Under pathological conditions, the expression of lncRNAs is frequently dysregulated. Recent studies demonstrated that lncRNAs significantly affect major cellular processes, and their aberrant expression is likely involved in the pathogenesis of various disorders. In this review, we will discuss the role of lncRNAs in the pathophysiology of psoriasis. We will summarize recent studies that investigated the relationships between lncRNAs and keratinocyte proliferation and pro-inflammatory responses.

Uncovering the Regulatory Role of Long Non-Coding RNAs in Colorectal Cancer Progression and Liver Metastasis: Implications for Therapeutic and Diagnostic Targeting

Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, largely due to metastasis, particularly to the liver, and the limited understanding of the molecular mechanisms underlying this process. In this study, we aimed to investigate the role of long non-coding Methods: RNAs (lncRNAs) are key regulatory factors in CRC progression and metastasis to liver tissues. Using high-throughput sequencing and microarray approaches, we analyzed gene expression profiles from two independent lncRNA datasets to identify potential players involved in liver metastasis. Results: Our findings revealed five lncRNAs—PROX1-AS1, SOX9-AS1, LINC01594, LINC01555, and APOA1-AS—previously known for their roles in CRC progression, now identified as being involved in the liver metastatic process. Additionally, 20 other lncRNAs, including VCAN-AS1, SYP-AS1, SMIM2-IT1, NCOA7-AS1, and LINC01449, were also identified as potential contributors to CRC liver metastasis. Notably, two lncRNAs—SATB2-AS1 and LINC01116—emerged as common candidates across both datasets, suggesting their significant role in promoting CRC metastasis to the liver. These two lncRNAs hold promise as molecular targets for therapeutic and diagnostic development. Conclusion: Our study uncovers a novel layer of regulatory mechanisms involving lncRNAs in CRC liver metastasis. These findings advance our understanding of the molecular behaviors that drive CRC progression and offer new avenues for targeted therapeutic strategies and diagnostic tools, particularly for liver metastasis in CRC.

Role of long non-coding RNAs and natural products in prostate cancer: insights into key signaling pathways.

Prostate cancer (PC) ranks among the most prevalent cancers in males. Recent studies have highlighted intricate connections between long non-coding RNAs (lncRNAs), natural products, and cellular signaling in PC development. LncRNAs, which are RNA transcripts without protein-coding function, influence cell growth, programmed cell death, metastasis, and resistance to treatments through pathways like PI3K/AKT, WNT/β-catenin, and androgen receptor signaling. Certain lncRNAs, including HOTAIR and PCA3, are associated with PC progression, with potential as diagnostic markers. Natural compounds, such as curcumin and resveratrol, demonstrate anticancer effects by targeting these pathways, reducing tumor growth, and modulating lncRNA expression. For instance, curcumin suppresses HOTAIR levels, hindering PC cell proliferation and invasion. The interaction between lncRNAs and natural compounds may open new avenues for therapy, as these substances can simultaneously impact multiple signaling pathways. These complex interactions offer promising directions for developing innovative PC treatments, enhancing diagnostics, and identifying new biomarkers for improved prevention and targeted therapy. This review aims to map the multifaceted relationship among natural products, lncRNAs, and signaling pathways in PC pathogenesis, focusing on key pathways such as AR, PI3K/AKT/mTOR, WNT/β-catenin, and MAPK, which are crucial in PC progression and therapy resistance. Regulation of these pathways by natural products and lncRNAs could lead to new insights into biomarker identification, preventive measures, and targeted PC therapies.

Stem cell status and prognostic applications of cuproptosis-associated lncRNAs in acute myeloid leukemia.

Acute myeloid leukemia (AML), a highly heterogeneous hematological malignancy, remains a major challenge in adult oncology. Stem cell research has highlighted the crucial role of long noncoding RNA (lncRNA) in regulating cellular differentiation and self-renewal processes, which are pivotal in AML pathogenesis and therapy resistance. This study explores the relationship between cuproptosis-related lncRNAs and AML prognosis, providing novel insights into their impact on hematopoietic stem and progenitor cells. We collected clinical information from 214 AML patients in our center and analyzed the association between granulocyte recovery after chemotherapy, cuproptosis, and prognosis. Additionally, we developed a prognostic model-the cuproptosis-associated long noncoding RNA prognostic model (CRLPM)-y analyzing data from The Cancer Genome Atlas (TCGA). Patients were stratified into high- and low-risk groups based on CRLPM, revealing significant survival differences. High-risk patients demonstrated lower sensitivity to chemotherapeutic agents such as Axitinib, GSK429286A, Navitoclax, and ZM-447439, underscoring the need for alternative therapeutic strategies. CRLPM offers a promising framework for integrating stem cell-focused approaches into personalized treatment regimens, paving the way for precision medicine in AML management.

Bibliometric analysis of glycolysis and prostate cancer research from 2004 to 2024

BackgroundProstate cancer (PCa) ranks as the second most common disease among men and the fourth most prevalent cancer worldwide. Enhanced glycolysis and excessive lactate secretion are recognized as critical factors driving the progression of various cancers. This study systematically investigated the research trends associated with glycolysis in PCa through bibliometric analysis.MethodIn this study, we conducted a systematic search of the Web of Science and PubMed databases for literature pertaining to the glycolysis of PCa that was published between January 1, 2004, and June 30, 2024. To achieve this objective, we employed CiteSpace software to generate visualizations that illustrate countries/regions, institutions, journals, and keywords. Additionally, we extracted pertinent quantitative data. Furthermore, we utilized VOSviewer software to create a collaboration network map among various journals.ResultsBetween 2004 and 2024, a total of 408 research articles on glycolysis in PCa were published, indicating a consistent upward trend in the annual publication rate. In this field, the United States not only leads in the volume of research papers but also has the highest degree of centrality. The journal "Cancer Research" is recognized as the most influential in the field, whereas "Prostate and Cancer" serves as a significant platform for disseminating research related to glycolysis in PCa. Keyword analysis has identified four primary research directions that have dominated this field over the past two decades. The role of glycolysis and its associated enzymes in PCa underpins this research. Glycolysis has also demonstrated significant clinical value in the diagnosis and prognosis of PCa. Moreover, drugs targeting glycolytic inhibitors and natural products have exhibited therapeutic potential against this disease. By modulating glycolytic mechanisms, there is potential to increase resistance in PCa. Currently, leading research in this area encompasses the application of nanotechnology to PCa glycolysis, the roles of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in this metabolic pathway, and the interactions between glycolysis and other biological processes in PCa.ConclusionThis study employs bibliometric analysis to provide a comprehensive overview of research on glycolysis in PCa over the past two decades. It highlights the current state of knowledge in this field, identifies key research hotspots, and explores emerging frontiers, particularly nanotechnology, lncRNA, and miRNA, which are driving innovative research directions.

The Role of Long Non-Coding RNA in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint damage and physical dysfunction. The pathogenesis of RA is highly complex, involving genetic, epigenetic, immune, and metabolic factors, among others. Over the years, research has highlighted the importance of non-coding RNAs (ncRNAs) in regulating gene expression. Given their dysregulation in numerous conditions, ncRNAs are thought to play a role in pathological processes. In RA, aberrant levels of circulating long ncRNAs (lncRNAs) are commonly observed in peripheral blood, along with their dysregulated expression in peripheral blood mononuclear cells and synovial tissue. This review discusses the involvement of lncRNAs in inflammation and the aggressive characteristics of fibroblast-like synoviocytes, a key cellular population driving RA progression.

The regulatory role and therapeutic potential of long non-coding RNA in non-small cell lung cancer.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype. Recent advances in transcriptome sequencing have highlighted the critical role of long non-coding RNAs (lncRNAs) in NSCLC, with lncRNAs influencing gene expression through epigenetic, transcriptional, and post-transcriptional mechanisms. Despite the growing understanding of lncRNAs, challenges such as delayed diagnosis and drug resistance continue to complicate NSCLC management. This review explores novel findings in the role of lncRNAs (e.g., MALAT1, HOTAIR, and GAS5) in NSCLC, with a particular focus on their encoded small peptides and N6-methyladenosine (m6A) modifications. We further discuss how the interplay between lncRNAs, their encoded peptides, and m6A modifications can provide new strategies for improving NSCLC diagnosis, treatment, and overcoming drug resistance. This review also highlights emerging research avenues that could lead to innovative clinical interventions in NSCLC.

Epigenetic Role of Long Non-coding RNAs in Multiple Myeloma.

This review aims to explore the pivotal role of long non-coding RNAs (lncRNAs) as epigenetic regulators in the pathogenesis of multiple myeloma (MM). Additionally, we have portrayed the dual role of lncRNAs in the epigenetic landscape of MM pathobiology. In MM, lncRNAs are pivotal for proliferation, progression, and drug resistance by acting as miRNA sponges, regulating mRNA activity through microRNA recognition elements (MREs). Epigenetic modifications in lncRNAs influence gene expression, with some like MEG3, GAS5, CRNDE, and H19 showing promoter hypermethylation, while MALAT1 exhibits hypomethylation. Targeting lncRNAs using siRNA, ASO, CRISPR-Cas9, or small molecule inhibitors shows promise in preclinical studies, alongside the potential benefits of epigenetic-based therapies such as DNMTi and HDACi. Clinical trials combining epigenetic modifiers with standard chemotherapy show encouraging results, especially in relapsed/refractory MM. The key finding of the studies highlighted in the review paves the way for understanding the epigenetic role of lncRNAs in MM disease progression and biology. In addition, the novel therapeutic strategies that have shown promising results have been highlighted. The adoption of the epigenetic landscape into therapeutics in addition to existing treatment strategies may increase the efficacy of treatment approaches.

LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 Axis.

Osteoarthritis (OA) is a leading cause of pain, disability, and reduced mobility worldwide, characterized by metabolic imbalances in chondrocytes, extracellular matrix (ECM), and subchondral bone. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in OA pathogenesis. This study focuses on lncRNA PTS-1, a novel lncRNA, to explore its function and regulatory mechanisms in OA progression. The expression profile of lncRNAs was assessed using RNA sequencing and qRT-PCR. The expression of lnc-PTS-1 was further validated by qRT-PCR in degenerated cartilage tissues, degenerative primary chondrocytes, and IL-1β-treated C28/I2 cells. Cell viability, proliferation, and apoptosis rates, along with the mRNA and protein levels of apoptosis-related markers (cleaved Caspase 3, cleaved Caspase 9, Bcl-2, Bax), ECM metabolism markers (MMP-3, MMP-13, aggrecan, collagen II), and inflammation-related markers (IL-1β, IL-6, TNF-α) were evaluated using Cell Counting Kit-8, Toluidine Blue staining, Alcian Blue staining, flow cytometry, qRT-PCR, immunofluorescence, and Western Blot. The interaction between miR-8085 and lnc-PTS-1 or E2F2 was investigated through dual luciferase reporter assays and RNA immunoprecipitation (RIP) analyses. Lnc-PTS-1 expression was significantly downregulated in degenerated cartilage tissues, IL-1β-induced degenerative primary chondrocytes and C28/I2 cells. Functional experiments showed that lnc-PTS-1 knockdown aggravated IL-1β-induced ECM degradation, chondrocyte apoptosis, and inflammation, while its overexpression provided protective effects. Mechanistically, lnc-PTS-1 acted as a competing endogenous RNA (ceRNA) by sponging miR-8085, thereby upregulating E2F2 expression. Notably, miR-8085 upregulation diminished the protective effects of lnc-PTS-1 on ECM degradation, apoptosis, and inflammation, while E2F2 upregulation partially alleviated IL-1β-induced damage. However, these mitigating effects were reversed by miR-8085 overexpression. These findings identify lnc-PTS-1/miR-8085/E2F2 axis as a novel regulatory mechanism in OA pathogenesis, providing theoretical basis and experimental evidence for the potential clinical application of new lncRNA molecules in the treatment of OA.

Potential role of long noncoding RNA maternally expressed gene 3 (MEG3) in the process of neurodegeneration.

Neurodegenerative diseases (ND) are complex diseases of still unknown etiology. Lately, long non-coding RNAs (lncRNAs) have become increasingly popular and implicated in several pathologies as they have several roles and appear to be involved in all biological processes such as cell signaling and cycle control as well as translation and transcription. MEG3 is one of these and acts by binding proteins or directly or competitively binding miRNAs. It has a crucial role in controlling cell death, inflammatory process, oxidative stress, endoplasmic reticulum stress, epithelial-mesenchymal transition and other processes. Recent reports showed that MEG3 is a major driving force of the necrosis phenomena in AD, causing the death of neurons, and its upregulation in cancer patients was linked to tumor suppression. Dysregulation of MEG3 affects neuronal cell death, inflammatory process, smooth muscle cell proliferation and consequently leads to the initiation or the acceleration of the disease. This review examines the current state of knowledge concerning the level of expression and the regulatory function of MEG3 in relation to several NDs. In addition, we examined the relation of MEG3 with neurotrophic factors such as Tumor growth factor β (TGFβ) and its possible mechanism of action. A comprehensive and in-depth analysis of the role of MEG3 in ND could give a clearer picture about the initiation of the process of neuronal death and help develop an alternative therapy that targets MEG3.

Regulating the regulators: long non-coding RNAs as autophagic controllers in chronic disease management.

The increasing prevalence of chronic diseases and their associated morbidities demands a deeper understanding of underlying mechanism and causative factors, with the hope of developing novel therapeutic strategies. Autophagy, a conserved biological process, involves the degradation of damaged organelles or protein aggregates to maintain cellular homeostasis. Disruption of this crucial process leads to increased genomic instability, accumulation of reactive oxygen species(ROS), decreased mitochondrial functions, and suppression of ubiquitination, leading to overall decline in quality of intracellular components. Such deregulation has been implicated in a wide range of pathological conditions such as cancer, cardiovascular, inflammatory, and neurological disorders. This review explores the role of long non-coding RNAs (lncRNAs) as modulators of transcriptional and post-transcriptional gene expression, regulating diverse physiological process like proliferation, development, immunity, and metabolism. Moreover, lncRNAs are known to sequester autophagy related microRNAs by functioning as competing endogenous RNAs (ceRNAs), thereby regulating this vital process. In the present review, we delineate the multitiered regulation of lncRNAs in the autophagic dysfunction of various pathological diseases. Moreover, by highlighting recent findings on the modulation of lncRNAs in different stages of autophagy, and the emerging clinical landscape that recognizes lncRNAs in disease diagnosis and therapy, this review highlights the potential of lncRNAs as biomarkers and therapeutic targets in clinical settings of different stages of autophagic process by regulating ATG and its target genes. This focus on lncRNAs could lead to breakthroughs in personalized medicine, offering new avenues for diagnosis and treatment of complex diseases.

The oncogenic lncRNA MIR503HG suppresses cellular senescence counteracting supraphysiological androgen treatment in prostate cancer

BackgroundThe androgen receptor (AR), a ligand-dependent transcription factor, plays a key role in regulating prostate cancer (PCa) growth. The novel bipolar androgen therapy (BAT) uses supraphysiological androgen levels (SAL) that suppresses growth of PCa cells and induces cellular senescence functioning as a tumor suppressive mechanism. The role of long non-coding RNAs (lncRNAs) in the regulation of SAL-mediated senescence remains unclear. This study focuses on the SAL-repressed lncRNA MIR503HG, examining its involvement in androgen-controlled cellular senescence in PCa.MethodsTranscriptome and ChIP-Seq analyses of PCa cells treated with SAL were conducted to identify SAL-downregulated lncRNAs. Expression levels of MIR503HG were analyzed in 691 PCa patient tumor samples, mouse xenograft tumors and treated patient-derived xenografts. Knockdown and overexpression experiments were performed to assess the role of MIR503HG in cellular senescence and proliferation using senescence-associated β-Gal assays, qRT-PCRs, and Western blotting. The activity of MIR503HG was confirmed in PCa tumor spheroids.ResultsA large patient cohort analysis shows that MIR503HG is overexpressed in metastatic PCa and is associated with reduced patient survival, indicating its potential oncogenic role. Notably, SAL treatment suppresses MIR503HG expression across four different PCa cell lines and patient-derived xenografts but interestingly not in the senescence-resistant LNCaP Abl EnzaR cells. Functional assays reveal that MIR503HG promotes PCa cell proliferation and inhibits SAL-mediated cellular senescence, partly through miR-424-5p. Mechanistic analyses and rescue experiments indicate that MIR503HG regulates the AKT-p70S6K and the p15INK4b-pRb pathway. Reduced expression of MIR503HG by SAL or knockdown resulted in decreased BRCA2 levels suggesting a role in DNA repair mechanisms and potential implications for PARP inhibitor sensitivity by SAL used in BAT clinical trial.ConclusionsThe lncRNA MIR503HG acts as an oncogenic regulator in PCa by repressing cellular senescence. SAL-induced suppression of MIR503HG enhances the tumor-suppressive effects of AR signaling, suggesting that MIR503HG could serve as a biomarker for BAT responsiveness and as a target for combination therapies with PARP inhibitors.

Prognostic value and immune landscapes of disulfidptosis‑related lncRNAs in bladder cancer.

Disulfidptosis, which was recently identified, has shown promise as a potential cancer treatment. Nonetheless, the precise role of long non-coding RNAs (lncRNAs) in this phenomenon is currently unclear. To elucidate their significance in bladder cancer (BLCA), a signature of disulfidptosis-related lncRNAs (DRlncRNAs) was developed and their potential prognostic significance was explored. BLCA sample data were sourced from The Cancer Genome Atlas. A predictive signature comprising DRlncRNAs was formulated and subsequently validated. The combination of this signature with clinical characteristics facilitated the development of a nomogram with practical clinical utility. Additionally, enrichment analysis was conducted, the tumor microenvironment (TME) was assessed, the tumor mutational burden (TMB) was analyzed, and drug sensitivity was explored. Reverse transcription-quantitative PCR (RT-qPCR) was utilized to quantify lncRNA expression. The results revealed an eight-gene signature based on DRlncRNAs was established, and the predictive accuracy of the nomogram that incorporated the risk score [area under the curve (AUC)=0.733] outperformed the nomogram without it (AUC=0.703). High-risk groups were associated with pathways such as WNT signaling, focal adhesion and cell cycle pathways. The TME study revealed that high-risk patients had increased immune infiltration, whereas the TMB and tumor immune dysfunction and exclusion scores in low-risk patients indicated a potentially robust immune response. Drug sensitivity analysis identified appropriate antitumor drugs for each group. RT-qPCR experiments validated significant differences in DRlncRNAs expression between normal and BLCA cell lines. In conclusion, the prognostic risk signature, which includes the eight identified DRlncRNAs, demonstrates promise for predicting prognosis of patients with BLCA and guiding the selection of suitable immunotherapy and chemotherapy strategies.

Uncovering the key lncRNAs in regulating cadmium accumulation and translocation in sweet sorghum.

1988 lncRNAs were identified in sweet sorghum roots under cadmium treatment; lncRNA 15962 and lncRNA 11558 were validated to be the key lncRNAs involved in regulating cadmium accumulation and translocation. Cadmium (Cd) has become one of the most harmful and widespread pollutants with industry development. Sweet sorghum is an ideal plant for phytoremediation of Cd-contaminated soil. However, little is known about the regulatory role of long non-coding RNAs (lncRNAs) associated with Cd stress response in sweet sorghum. Here, lncRNA-seq was carried out in the roots of two contrasting sweet sorghum genotypes (high-Cd accumulation genotype 'H18', and low-Cd accumulation genotype 'L69'). A total of 1988 lncRNAs were characterized, including 52 and 69 differentially expressed lncRNAs in 'H18' and 'L69' in response to Cd stress, respectively. Furthermore, the trans- or cis-target genes of lncRNAs were investigated. Then, 65 lncRNAs were characterized as the probable target of 117 miRNAs and 1888 genes were identified as putative cis-target genes of Cd-responsive lncRNAs. The dual-luciferase reporter assay indicated lncRNA 15962 may serve as the endogenous target mimics of sbi-miR5565e, which targeted two genes (Sobic.005G212900 and Sobic.009G144700) involved in cell wall metabolism. Fourcis-target genes includingSbYS1which encoding a Cd chelate transporter, were up-regulated by overexpression of their corresponding lncRNAs in sweet sorghum protoplasts, suggesting the positive regulatory role of lncRNAs to thesecis-target genes. Moreover, the expression ofSbYS1decreasedwhenlncRNA11558was inhibited by exogenous miRNA application in 'H18' seedlings, further demonstrating the positive regulatory role of lncRNA11558toSbYS1. Altogether, our findings shed light on the regulatory role of lncRNAs associated with Cd accumulation and translocation in sweet sorghum.