Role Of Long Non-coding RNAs Research Articles

The role of long non-coding RNAs in the development of diabetic kidney disease and the involved clinical application.

Diabetic kidney disease (DKD), one of the common microvascular complications of diabetes, is increasing in prevalence worldwide and can lead to End-stage renal disease. However, there are still gaps in our understanding of the pathophysiology of DKD, and both current clinical diagnostic methods and treatment strategies have drawbacks. According to recent research, long non-coding RNAs (lncRNAs) are intimately linked to the developmental process of DKD and could be viable targets for clinical diagnostic decisions and therapeutic interventions. Here, we review recent insights gained into lncRNAs in pathological changes of DKD such as mesangial expansion, podocyte injury, renal tubular injury, and interstitial fibrosis. We also discuss the clinical applications of DKD-associated lncRNAs as diagnostic biomarkers and therapeutic targets, as well as their limitations and challenges, to provide new methods for the prevention, diagnosis, and treatment of DKD.

LncRNA Myocardial Infarction-Associated Transcript (MIAT)/miR-505-5p Axis Regulates Proliferation and Migration of Vascular Smooth Muscle Cells of Hypertension Mice

To clarify the role of long non-coding RNA (lncRNA) MIAT in regulating proliferative and migratory abilities in VSMCs extracted from hypertension mice via downregulating microRNA-505-5p (miR-505-5p). Serum levels of MIAT and miR-505-5p in enrolled 20 hypertension patients and 20 healthy volunteers were detected. VSMCs were extracted from hypertension mice and healthy mice. Regulatory effects of MIAT and miR-505-5p on proliferative and migratory abilities in VSMCs were examined. At last, the interaction between MIAT and miR-505-5p was explored by dual-luciferase reporter assay and rescue experiments. Serum level of MIAT was higher in hypertension patients than those of healthy subjects, while miR-505-5p was downregulated. MIAT level was negatively correlated to miR-505-5p level in serum of hypertension patients. Knockdown of MIAT suppressed proliferative and migratory abilities in VSMCs extracted from hypertension mice. In addition, knockdown of MIAT upregulated E-cadherin and downregulated Vimentin and Snail-1. MiR-505-5p was verified to be the target binding MIAT. Knockdown of miR-505-5p reversed regulatory effects of MIAT on VSMCs phenotypes. LncRNA MIAT stimulates VSMCs in hypertension mice to proliferate and migrate through downregulating miR-505-5p, which may be a promising target for diagnosis and treatment of hypertension.

Emerging roles of long non-coding RNAs in human epilepsy.

Genome-scale biological studies conducted in the post-genomic era have revealed that two-thirds of human genes do not encode proteins. Most functional non-coding RNA transcripts in humans are products of long non-coding RNA (lncRNA) genes, an abundant but still poorly understood class of human genes. As a result of their fundamental and multitasking regulatory roles, lncRNAs are associated with a wide range of human diseases, including neurological disorders. Approximately 40% of lncRNAs are specifically expressed in the brain, and many of them exhibit distinct spatiotemporal patterns of expression. Comparative genomics approaches have determined that 65%-75% of human lncRNA genes are primate-specific and hence can be posited as a contributing potential cause of the higher-order complexity of primates, including human, brains relative to those of other mammals. Although lncRNAs present important mechanistic examples of epileptogenic functions, the human/primate specificity of lncRNAs questions their relevance in rodent models. Here, we present an in-depth review that supports the contention that human lncRNAs are direct contributors to the etiology and pathogenesis of human epilepsy, as a means to accelerate the integration of lncRNAs into clinical practice as potential diagnostic biomarkers and therapeutic targets. Meta-analytically, the major finding of our review is the commonality of lncRNAs in epilepsy and cancer pathogenesis through mitogen-activated protein kinase (MAPK)-related pathways. In addition, neuroinflammation may be a relevant part of the common pathophysiology of cancer and epilepsy. LncRNAs affect neuroinflammation-related signaling pathways such as nuclear factor kappa- light- chain- enhancer of activated B cells (NF-κB), Notch, and phosphatidylinositol 3- kinase/ protein kinase B (Akt) (PI3K/AKT), with the NF-κB pathway being the most common. Besides the controversy over lncRNA research in non-primate models, whether neuroinflammation is triggered by injury and/or central nervous system (CNS) toxicity during epilepsy modeling in animals or is a direct consequence of epilepsy pathophysiology needs to be considered meticulously in future studies.

Predictive significance of glycolysis-associated lncRNA profiles in colorectal cancer progression

BackgroundThe Warburg effect is a hallmark characteristic of colorectal cancer (CRC). Despite extensive research, the role of long non-coding RNAs (lncRNAs) in influencing the Warburg effect remains incompletely understood. Our study aims to identify lncRNAs that may modulate the Warburg effect by functioning as competing endogenous RNAs (ceRNAs).MethodsUtilizing bioinformatics approaches, we extracted glycolysis-associated gene data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and identified 101 glycolysis-related lncRNAs in CRC. We employed Univariable Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, and Multivariable Cox regression to develop a prognostic model comprising four glycolysis-linked lncRNAs. We then constructed a prognostic nomogram integrating this lncRNA model with other relevant clinical parameters.ResultsThe prognostic efficacy of our four-lncRNA signature and its associated nomogram was validated in both training and validation cohorts. Functional assays demonstrated significant glycolysis and hexokinase II (HK2) inhibition following the silencing of RUNDC3A − AS1, a key lncRNA in our prognostic signature, highlighting its regulatory importance in the Warburg effect.ConclusionsOur research illuminates the critical role of glycolysis-centric lncRNAs in CRC. The developed prognostic model and nomogram underscore the pivotal prognostic and regulatory significance of the lncRNA RUNDC3A − AS1 in the Warburg effect in colorectal cancer.

Biological functions of PCAT-1/ SOX4 in cell proliferation and invasion of breast cancer.

Breast cancer (BC) is one of the most common fatal cancers. Recent studies have identified the vital role of long noncoding RNA (lncRNAs) in the development and progression of BC. In this research, lncRNA PCAT-1 was studied to identify how it functioned in the metastasis of BC. PCAT-1 expression of tissues was detected by real-time quantitative polymerase chain reaction (RT-qPCR) in 50 BC patients. Cell proliferation, wound healing assay and transwell assay were used to observe the biological behavior changes of BC cells through knockdown or overexpression of PCAT-1. In addition, RT-qPCR and Western blot assay were performed to discover the potential target protein of PCAT-1 in BC. PCAT-1 expression level in BC samples was higher than that of adjacent ones. Besides, cell proliferation, migrated ability and cell invaded ability of BC cells were inhibited after PCAT-1 was silenced. Cell proliferation, migration and invasion of BC cells were promoted after PCAT-1 was overexpressed. In addition, SOX4 was downregulated after silence of PCAT-1 in BC cells, while SOX4 was upregulated after overexpression of PCAT-1 in BC cells. Furthermore, SOX4 was upregulated in BC tissues and was positively associated with PCAT-1. Our study uncovers a new oncogene in BC and suggests that PCAT-1 could enhance BC cell proliferation, migration and invasion via targeting SOX4, which provided a novel therapeutic target for BC patients.

The roles of long non-coding RNAs in ovarian cancer: from functions to therapeutic implications

Long non-coding RNAs (lncRNAs) are multifunctional and participate in a variety of biological processes and gene regulatory networks. The deregulation of lncRNAs has been extensively implicated in diverse human diseases, especially in cancers. Overwhelming evidence demonstrates that lncRNAs are essential to the pathophysiological processes of ovarian cancer (OC), acting as regulators involved in metastasis, cell death, chemoresistance, and tumor immunity. In this review, we illustrate the expanded functions of lncRNAs in the initiation and progression of OC and elaborate on the signaling pathways in which they pitch. Additionally, the potential clinical applications of lncRNAs as biomarkers in the diagnosis and treatment of OC were emphasized, cementing the bridge of communication between clinical practice and basic research.

Long non-coding RNA SOX2OT in tamoxifen-resistant breast cancer.

Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan-Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.

The Role of Long Non-Coding RNAs in Vascular Smooth Muscle Cell Phenotype and the Pathogenesis of Cardiovascular and Cerebrovascular Aneurysms

The Role of Long Non-Coding RNAs in Vascular Smooth Muscle Cell Phenotype and the Pathogenesis of Cardiovascular and Cerebrovascular Aneurysms

Diagnostic and prognostic role of long non-coding RNAs (lncRNAs) in metastatic melanoma patients with BRAF gene mutation receiving BRAF and MEK inhibitors

Melanoma is a cancer with a high incidence rate that, despite the significant development of therapeutic options, still remains a major problem. The identification of biomarkers to select the right therapy for the right patient is one of the possibilities to improve the prognosis of patients. Potentially, the function of biomarkers could be played long non-coding RNAs (lncRNAs). The expression of selected 90 lncRNAs in serum from 30 metastatic melanoma patients with confirmed mutations in the BRAF V600 E or K gene was studied. Serum was collected prior to BRAF and MEK inhibitor therapy. The control group consisted of 16 healthy volunteers. A total of 41 lncRNAs were identified the expression of which differed statistically significantly between the patient group and the healthy volunteers. In addition, it was shown that the expression of HOXA3as (p = 0.033), PRINS (p = 0.036) and RNCR3 (p = 0.045) is higher in patients with the presence of CNS metastases, PFS inhibiting RNA (p = 0.048) is higher among patients with the presence of hepatic metastases, UCA1 (p = 0.008) expression is lower in patients with increased lactate dehydrogenase levels, while HOTAIRM1 (p = 0.044) and E2F4 antisense (p = 0.040) expression is lower in patients over 60 years of age. In addition, patients with high lincRNASFMBT2 expression showed longer median PFS (8.75 vs. 17.5 months, p = 0.0319) and OS (9.75 vs. 38 months (open observation, p = 0.0253). The obtained results require validation on a larger group of patients. If the results are confirmed, the indicated lncRNAs may play an important role as diagnostic and prognostic markers.

Identification and validation of tryptophan metabolism-related lncRNAs in lung adenocarcinoma prognosis and immune response

BackgroundTryptophan (Trp) is an essential amino acid. Increasing evidence suggests that tryptophan metabolism plays a complex role in immune escape from Lung adenocarcinoma (LUAD). However, the role of long non-coding RNAs (lncRNAs) in tryptophan metabolism remains to be investigated.MethodsThis study uses The Cancer Genome Atlas (TCGA)-LUAD dataset as the training cohort, and several datasets from the Gene Expression Omnibus (GEO) database are merged into the validation cohort. Genes related to tryptophan metabolism were identified from the Molecular Signatures Database (MSigDB) database and further screened for lncRNAs with Trp-related expression. Subsequently, a prognostic signature of lncRNAs related to tryptophan metabolism was constructed using Cox regression analysis, (Least absolute shrinkage and selection operator regression) and LASSO analysis. The predictive performance of this risk score was validated by Kaplan–Meier (KM) survival analysis, (receiver operating characteristic) ROC curves, and nomograms. We also explored the differences in immune cell infiltration, immune cell function, tumor mutational load (TMB), tumor immune dysfunction and exclusion (TIDE), and anticancer drug sensitivity between high- and low-risk groups. Finally, we used real-time fluorescence quantitative PCR, CCK-8, colony formation, wound healing, transwell, flow cytometry, and nude mouse xenotransplantation models to elucidate the role of ZNF8-ERVK3-1 in LUAD.ResultsWe constructed 16 tryptophan metabolism-associated lncRNA prognostic models in LUAD patients. The risk score could be used as an independent prognostic indicator for the prognosis of LUAD patients. Kaplan–Meier survival analysis, ROC curves, and risk maps validated the prognostic value of the risk score. The high-risk and low-risk groups showed significant differences in phenotypes, such as the percentage of immune cell infiltration, immune cell function, gene mutation frequency, and anticancer drug sensitivity. In addition, patients with high-risk scores had higher TMB and TIDE scores compared to patients with low-risk scores. Finally, we found that ZNF8-ERVK3-1 was highly expressed in LUAD tissues and cell lines. A series of in vitro experiments showed that knockdown of ZNF8-ERVK3-1 inhibited cell proliferation, migration, and invasion, leading to cell cycle arrest in the G0/G1 phase and increased apoptosis. In vivo experiments with xenografts have shown that knocking down ZNF8-ERVK3-1 can significantly inhibit tumor size and tumor proliferation.ConclusionWe constructed a new prognostic model for tryptophan metabolism-related lncRNA. The risk score was closely associated with common clinical features such as immune cell infiltration, immune-related function, TMB, and anticancer drug sensitivity. Knockdown of ZNF8-ERVK3-1 inhibited LUAD cell proliferation, migration, invasion, and G0/G1 phase blockade and promoted apoptosis.

A novel long non-coding RNA LINC00524 facilitates invasion and metastasis through interaction with TDP43 in breast cancer.

Breast cancer (BC) remains a significant health concern worldwide, with metastasis being a primary contributor to patient mortality. While advances in understanding the disease's progression continue, the underlying mechanisms, particularly the roles of long non-coding RNAs (lncRNAs), are not fully deciphered. In this study, we examined the influence of the lncRNA LINC00524 on BC invasion and metastasis. Through meticulous analyses of TCGA and GEO data sets, we observed a conspicuous elevation of LINC00524 expression in BC tissues. This increased expression correlated strongly with a poorer prognosis for BC patients. A detailed Gene Ontology analysis suggested that LINC00524 likely exerts its effects through RNA-binding proteins (RBPs) mechanisms. Experimentally, LINC00524 was demonstrated to amplify BC cell migration, invasion and proliferation invitro. Additionally, invivo tests showed its potent role in promoting BC cell growth and metastasis. A pivotal discovery was LINC00524's interaction with TDP43, which leads to the stabilization of TDP43 protein expression, an element associated with unfavourable BC outcomes. In essence, our comprehensive study illuminates how LINC00524 accelerates BC invasion and metastasis by binding to TDP43, presenting potential avenues for therapeutic interventions.

Investigating diagnostic potential of long non-coding RNAs in head and neck squamous cell carcinoma using TCGA database and clinical specimens

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and prognostically challenging cancer worldwide. The role of long non-coding RNAs (lncRNAs) in cancer regulation is progressively being understood. This study aims to identify lncRNAs with diagnostic potential as biomarkers for HNSCC. Statistical analysis was performed on expression data from the Cancer Genome Atlas (TCGA) database to identify potential lncRNAs associated with HNSCC. Four selected lncRNAs were validated using real-time quantitative reverse transcription polymerase chain reaction and correlated with clinical factors. Functional roles were further investigated. A total of 488 differentially expressed lncRNAs were identified in TCGA-HNSC. After rigorous evaluation based on p-values, survival analysis, and ROC analysis, 24 lncRNAs were prioritized for additional investigation. LINC00460, LINC00941, CTC-241F20.4, and RP11-357H14.17 were established as candidate diagnostic biomarkers. These lncRNAs exhibited elevated expression in HNSCC tissues and were associated with poor prognosis. Combining them showed high diagnostic accuracy. Notably, LINC00460 and CTC-241F20.4 demonstrated a significant elevation in the advanced stages of HNSCC. We constructed an lncRNA-mRNA regulatory network, and the array of significant regulatory pathways identified included focal adhesion, regulation of epithelial cell migration, and others. Additionally, these lncRNAs were found to influence immune responses by modulating immune cell infiltration in the HNSCC microenvironment. Our research indicates that LINC00460, LINC00941, RP11-357H14.17, and CTC-241F20.4 may have diagnostic and prognostic importance in HNSCC. Furthermore, we have gained insights into their potential functional roles, particularly about immune responses and interactions in the microenvironment.

LncRNA SNHG26 promotes gastric cancer progression and metastasis by inducing c-Myc protein translation and an energy metabolism positive feedback loop

Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial–mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.

A novel perspective on the role of long non-coding RNAs in regulating polyphenols biosynthesis in methyl jasmonate-treated Siraitia grosvenorii suspension cells

Siraitia grosvenorii (S. grosvenorii) is considered a promising economic crop due to its various bioactive compounds. Polyphenols, one of the main bioactive compounds in S. grosvenorii suspension cells, are highly beneficial for human health. Therefore, elucidating their biosynthetic regulatory mechanisms is crucial for the efficient production of these bioactive compounds. Previous studies on the regulation of plant bioactive components have more often focused on the role of protein-coding genes but overlooked non-coding genes. In this study, we provide a novel perspective on the role of long non-coding RNAs (lncRNAs) in regulating polyphenols biosynthesis in methyl jasmonate (125 µM)-treated S. grosvenorii cells. Firstly, metabolomics analysis revealed 70 differential metabolites mainly composed of polyphenols (phenolic acids and flavonoids) in the cells. The intracellular polyphenols content (maximum 41.12 mg g−1) increased synchronously with the upregulation of polyphenols biosynthetic enzyme activity. Secondly, transcriptomics analysis indicated 496 differentially-expressed lncRNAs and 3595 differentially-expressed mRNAs in the cells. Besides, 29 putative regulatory pairs between differentially-expressed lncRNAs and their target mRNAs were identified, which might affect plant signal transduction, polyphenols and their precursors biosynthesis, and related transport pathways, ultimately mediating the accumulation of polyphenols in the cells. Finally, using an efficient transient transformation strategy established in this study, an antisense-lncRNA of phenylalanine ammonia-lyase (lnc-PAL) was preliminarily proven to be a negative regulatory factor on polyphenols biosynthesis in S. grosvenorii. Therefore, our findings expanded the knowledge of lncRNAs in polyphenols biosynthesis, providing a theoretical basis for the efficient production of these compounds in S. grosvenorii cells.

Abstract 5684: The role of the lncRNA Slamon and Slc25a13 neighbor gene in melanoma aggressiveness

Abstract Melanomas are responsible for about 80% of all deaths related to skin cancers. This is due to its high potential of metastasizing and developing resistance to treatments. Novel therapeutic modalities and the identification of biomarkers able to predict the prognosis are necessary. Studies have revealed the central role of long non-coding RNAs (lncRNAs) in regulatory networks controlling cell behavior. The disruption of these regulatory networks as a consequence of altered expression of lncRNAs can contribute to cancer development and progression. Our laboratory has developed a linear cellular model of melanoma progression consisting of distinct cell lines: melan-a (melanocytes), 4C (pre-malignant melanocytes), 4C11- (undifferentiated, slow-growing and non-metastatic melanoma cells) and 4C11+ (differentiated, highly proliferative and metastatic melanoma cells), which were analyzed for their lncRNA expression profile. Differentially expressed lncRNAs identified by RNAseq were selected by in silico analyses based on their proximity to differentially expressed coding-genes in the same melanoma model. Correlation analyses were performed between the expression of differentially expressed lncRNA neighboring genes and their melanoma patient survival, using two independent melanoma cohorts (TCGA and Leeds). Among those lncRNA located near genes presenting prognostic value is the lncRNA Gm20619, here named Slamon, neighbor to Slc25a13 gene (mitochondrial aspartate/glutamate carrier gene), which high expression correlates with poor prognosis. Both Slamon lncRNA and Slc25a13 are highly expressed in the metastatic melanoma cells 4C11+ compared to melan-a, 4C and 4C11- cell lines. The knocking down of Slamon or Slc25a13 were performed in 4C11+ melanoma cells, followed by analyses of collective migration, clonogenicity, proliferation, anoikis resistance, and dacarbazine and MEK inhibitor treatment. By knocking down Slamon lead 4C11+ cells significantly less migratory and less resistant to dacarbazine, and resulted in increased expression of Slc25a13 gene. 4C11+ melanoma cells knocked down for Slc25a13 also presented reduced migratory, clonogenicity, proliferation and anoikis resistance capability, diminished sensitivity to dacarbazine and MEK inhibitor treatment, and increased expression of Slamon lncRNA. The analysis of genes coexpressed with Slc25a13 revealed genes related to tumor progression, as Cdk15, Lsp1 and Pdgfrb. Our results suggest a crucial role of the lncRNA Slamon and Slc25a13 coding gene in melanoma progression which has never been described before. Slamon regulates tumor aggressiveness associated with Slc25a13, forming a regulatory network. These findings reveal the importance of lncRNAs in melanoma biology, potentially indicating transcripts that can serve as prognostic biomarkers and therapeutic targets in melanoma. Citation Format: Beatriz C. Tonin, Ana L. Ayub, André H. Lengert, Sang W. Han, Eduardo M. Reis, Frank J. Slack, Miriam G. Jasiulionis. The role of the lncRNA Slamon and Slc25a13 neighbor gene in melanoma aggressiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5684.

Abstract 5683: lncRNA-protein interactions that predict response to endocrine therapy in HR+ breast cancer

Abstract Hormone receptor positive (HR+) breast cancer (BCa) is the most frequently diagnosed BCa type accounting for 70% of all breast cancer cases. A large population of HR+ BCa patients (30-40%) are resistant to mainstay endocrine therapy and develop incurable metastatic disease. Hence, it is imperative to identify viable biomarkers that stratify patients as drug responders or non-responders. Emerging scientific literature highlights the essential role of long non-coding RNAs (lncRNA) in cancer drug resistance and metastatic transformation; lncRNA include RNAs over 200 nucleotides in length that do not encode protein. Major biological functions of lncRNA rely on association with select protein interactors. As lncRNA equally bind proteins with and without canonical RNA-binding motifs, it is unclear what facilitates this lncRNA-protein interaction. Our recent studies show that SUMO post-translational modification (or SUMOylation) of target proteins potentiates binding with lncRNA, particularly at the chromatin. Using a small-scale screening, we see that SUMO-modification works to enhance association with lncRNAs for proteins with and without a canonical RNA binding domain (RBD). SUMOylation of RBD-expressing heterochromatin protein 1 α (HP1α) drives interaction with multiple chromatin-associated lncRNA both within and outside canonical heterochromatin foci. Interaction with lncRNA supports SUMOylated HP1α’s unconventional function as a transcriptional repressor at select euchromatic loci. We now report an inverse relationship in which SUMOylated HP1α directs the stability of its lncRNA binding partner. Specifically, SUMO-modified HP1α directs cell-cycle dependent recruitment of the RNA degradation machinery to the chromatin and facilitates clearance of chromatin-bound lncRNA. This dynamic lncRNA degradation process is disturbed with cancer onset and instead favors aberrant cancer cell transformation. Consistently, restoring lncRNA degradation homeostasis decreases metastatic properties of HR+ BCa cells and increases sensitivity to targeted therapeutics currently in clinical trials. Our studies define a fundamental mechanism that dictates lncRNA stability and/or degradation in BCa cells. In addition, we present viable biomarkers that predict sensitivity to ET and alternative targeted therapies. Citation Format: Kacie D. Waiters, Maram Quttina, Ashfia F. Khan, Samaneh Karami, Anthony S. Peidl, Funmi Babajide, Tasneem Bawa-Khalfe. lncRNA-protein interactions that predict response to endocrine therapy in HR+ breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5683.

The crucial role of long non-coding RNAs in the pathogenesis, therapeutic response, and clinical implications of esophageal cancer

The crucial role of long non-coding RNAs in the pathogenesis, therapeutic response, and clinical implications of esophageal cancer

Competitive endogenous RNA networks: Decoding the role of long non-coding RNAs and circular RNAs in colorectal cancer chemoresistance.

Colorectal cancer (CRC) is recognized as one of the most common gastrointestinal malignancies across the globe. Despite significant progress in designing novel treatments for CRC, there is a pressing need for more effective therapeutic approaches. Unfortunately, many patients undergoing chemotherapy develop drug resistance, posing a significant challenge for cancer treatment. Non-coding RNAs (ncRNAs) have been found to play crucial roles in CRC development and its response to chemotherapy. However, there are still gaps in our understanding of interactions among various ncRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs). These ncRNAs can act as either oncogenes or tumour suppressors, affecting numerous biological functions in different cancers including CRC. A class of ncRNA molecules known as competitive endogenous RNAs (ceRNAs) has emerged as a key player in various cellular processes. These molecules form networks through lncRNA/miRNA/mRNA and circRNA/miRNA/mRNA interactions. In CRC, dysregulation of ceRNA networks has been observed across various cellular processes, including proliferation, apoptosis and angiogenesis. These dysregulations are believed to play a significant role in the progression of CRC and, in certain instances, may contribute to the development of chemoresistance. Enriching our knowledge of these dysregulations holds promise for advancing the field of diagnostic and therapeutic modalities for CRC. In this review, we discuss lncRNA- and circRNA-associated ceRNA networks implicated in the emergence and advancement of drug resistance in colorectal carcinogenesis.

Transcriptome-Wide 5-Methylcytosine Profiling of lncRNAs in the Mouse Cerebral Ischemia Model.

An increasing body of research has demonstrated the significant role of long non-coding RNAs (lncRNAs) in the pathogenesis of stroke. They can actively contribute to the disease's progression either by directly participating in its pathogenesis or by acting as mediators through competing endogenous RNA (ceRNA) mechanisms. Concurrently, epigenetics plays a pivotal role in the pathological mechanisms underlying stroke. Epigenetic factors serve as valuable markers for disease progression, diagnostic biomarkers, and novel therapeutic targets. One of the most prevalent epigenetic modifications is 5-methylcytosine (m5C). However, the specific profiles of 5-methylcytosine in lncRNAs associated with stroke remain to be solved. Within the scope of this research, we performed a thorough transcriptome-wide analysis of m5C methylation within lncRNAs by methylated RNA immunoprecipitation sequencing (MeRIP-Seq), within a mouse stroke model induced by middle cerebral artery occlusion. Our findings reveal substantial disparities in both the quantity and distribution of m5C within the mouse stroke model compared to normal mice. This suggests a potential linkage between stroke and lncRNA m5C modifications, offering valuable insights into the mechanisms of stroke pathogenesis and the development of new drug targets.

The Role of Long Noncoding RNAs (lncRNAs) in Esophageal Cancer Therapy Resistance and Metastasis.

Esophageal cancer (EC) is one of the most aggressive gastrointestinal cancers. Despite improvements in therapies, the survival rate of patients with EC remains low. Metastasis accounts for up to 90% of cancer-related deaths, and resistance to anti-neoplastic therapeutics is also a main cause of poor survival. Thus, metastasis and drug resistance are undoubtedly the two main challenges in cancer treatment. Among the different categories of noncoding RNAs, lncRNAs have historically drawn less attention. However, lncRNAs have gradually become a research hotspot, and increasing research has demonstrated that lncRNAs participate in the tumorigenesis of multiple types of cancer, including EC. Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides in length that play important roles in epigenetics, transcription regulation, and posttranscriptional processing. In this review, we elucidated the role of lncRNAs in the metastasis and drug resistance of EC and discussed their potential clinical applications and related limitations. With a better understanding of the underlying mechanisms of lncRNAs, we can identify therapeutic targets for EC in the future.