Value of long non-coding RNA HAS2-AS1 as a diagnostic and prognostic marker of glioma / El valor de ARNncl HAS2-AS1 como marcador diagnóstico y pronóstico del glioma

Background: Glioma presents high incidence and poor prognosis, and therefore more effective treatments are needed. Studies have confirmed that long non-coding RNAs (lncRNAs) basically regulate various human diseases including glioma. It has been theorized that HAS2-AS1 serves as an lncRNA to exert an oncogenic role in varying cancers. This study aimed to assess the value of lncRNA HAS2-AS1 as a diagnostic and prognostic marker for glioma. Methods: The miRNA expression data and clinical data of glioma were downloaded from the TCGA database for differential analysis and survival analysis. In addition, pathological specimens and specimens of adjacent normal tissue from 80 patients with glioma were used to observe the expression of HAS2-AS1. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic ability and prognostic value of HAS2-AS1 in glioma. Meanwhile, a Kaplan–Meier survival curve was plotted to evaluate the survival of glioma patients with different HAS2-AS1 expression levels. Results: HAS2-AS1 was significantly upregulated in glioma tissues compared with normal tissue. The survival curves showed that overexpression of HAS2-AS1 was associated with poor overall survival (OS) and progression-free survival (PFS). Several clinicopathological factors of glioma patients, including tumor size and WHO grade, were significantly correlated with HAS2-AS1 expression in tissues. The ROC curve showed an area under the curve (AUC) value of 0.863, indicating that HAS2-AS1 had good diagnostic value. The ROC curve for the predicted OS showed an AUC of 0.906, while the ROC curve for predicted PFS showed an AUC of 0.88. Both suggested that overexpression of HAS2-AS1 was associated with poor prognosis.Conclusions: Normal tissues could be clearly distinguished from glioma tissues based on HAS2-AS1 expression. Moreover, overexpression of HAS2-AS1 indicated poor prognosis in glioma patients.(AU)

Introducción: Los gliomas presentan una alta incidencia y un mal pronóstico, por lo que es necesario un tratamiento más efectivo. Algunos estudios han confirmado que los ARN no codificantes de cadena larga (ARNncl) regulan diferentes enfermedades, entre las que se incluyen los gliomas. Se ha postulado que HAS2-AS1 actúa como un ARNncl, con un efecto oncogénico en diferentes tipos de cáncer. Este estudio tiene como objetivo analizar el valor del ARNncl HAS2-AS1 como marcador diagnóstico y pronóstico de glioma. Métodos: Descargamos los datos clínicos y de expresión de micro-ARN de la base de datos del Atlas del Genoma del Cáncer (TCGA) para realizar el análisis diferencial y de supervivencia. También analizamos la expresión de HAS2-AS1 en muestras patológicas y muestras de tejido adyacente normal de 80 pacientes con glioma. Para analizar la capacidad diagnóstica y el valor pronóstico de HAS2-AS1 en el glioma, recurrimos a la curva ROC. También utilizamos curvas de Kaplan-Meier para evaluar la supervivencia de los pacientes con glioma con diferentes niveles de expresión de HAS2-AS1. Resultados: La expresión de HAS2-AS1 era significativamente mayor en las muestras patológicas que en el tejido normal. Las curvas de supervivencia demostraron que la sobreexpresión de HAS2-AS1 estaba relacionada con una menor supervivencia general y supervivencia libre de progresión. Algunos factores clínico-patológicos de los pacientes con glioma, como el tamaño del tumor y su grado, según la clasificación de la OMS, mostraron una correlación significativa con la expresión de HAS2-AS1 en los tejidos afectados. La curva ROC mostró un área bajo la curva de 0,863, lo que indica que la expresión de HAS2-AS1 posee un importante valor diagnóstico. El área bajo la curva de la supervivencia general estimada fue de 0,906; para la supervivencia libre de progresión estimada, de 0,88. Ambos valores muestran que la sobreexpresión de HAS2-AS1 se asocia con un mal pronóstico...(AU)

Enhancing m6A modification of lncRNA through METTL3 and RBM15 to promote malignant progression in bladder cancer.

Objective: Bladder cancer is one of the most prominent malignancies affecting the urinary tract, characterized by a poor prognosis. Our previous research has underscored the pivotal role of m6A methylation in the progression of bladder cancer. Nevertheless, the precise relationship between N6-methyladenosine (m6A) regulation of long non-coding RNA (lncRNA) and bladder cancer remains elusive. Methods: This study harnessed sequencing data and clinical records from 408 bladder cancer patients in the TCGA database. Employing R software, we conducted bioinformatics analysis to establish an m6A-lncRNA co-expression network. Analyzing the differences between high and low-risk groups, particularly at the immunological level, and subsequently investigating the primary regulatory factors of these lncRNA, validating the findings through experiments, and exploring their specific cellular functions. Results: We identified 50 m6A-related lncRNA with prognostic significance through univariate Cox regression analysis. In parallel, we employed a LASSO-Cox regression model to pinpoint 11 lncRNA and calculate risk scores for bladder cancer patients. Based on the median risk score, patients were categorized into low-risk and high-risk groups. The high-risk cohort exhibited notably lower survival rates than their low-risk counterparts. Further analysis pointed to RBM15 and METTL3 as potential master regulators of these m6A-lncRNA. Experimental findings also shed light on the upregulated expression of METTlL3 and RBM15 in bladder cancer, where they contributed to the malignant progression of tumors. The experimental findings demonstrated a significant upregulation of METTL3 and RBM15 in bladder cancer specimens, implicating their contributory role in the oncogenic progression. Knockdown of METTL3 and RBM15 resulted in a marked attenuation of tumor cell proliferation, invasion, and migration, which was concomitant with a downregulation in the cellular m6A methylation status. Moreover, these results revealed that RBM15 and METTL3 function in a synergistic capacity, positing their involvement in cancer promotion via the upregulation of m6A modifications in long non-coding RNAs. Additionally, this study successfully developed an N-methyl-N-nitrosourea (MNU)-induced rat model of in situ bladder carcinoma, confirming the elevated expression of RBM15 and METTL3, which paralleled the overexpression of m6A-related- lncRNAs observed in bladder cancer cell lines. This congruence underscores the potential utility of these molecular markers in in vivo models that mirror human malignancies. Conclusion: This study not only offers novel molecular targets,but also enriches the research on m6A modification in bladder cancer, thereby facilitating its clinical translation.

Qntrolling the LncRNA HULC-Tregs-PD-1 axis inhibits immune escape in the tumor microenvironment.

Background: Immune escape remains a major challenge in the treatment of malignant tumors. Here, we studied the mechanisms underlying immune escape in the tumor microenvironment and identified a potential therapeutic target. Methods: Pathological specimens from patients with liver cancer, soft tissue sarcoma, and liver metastasis of colon cancer were subjected to immunohistochemistry analysis to detect the expression of programmed death-1 (PD-1) in the tumor microenvironment (TME). Additionally, the expression of regulatory T cells (Tregs) and long non-coding RNAs (lncRNAs), such as highly upregulated in liver cancer (HULC) was evaluated by fluorescence in situ hybridization, and the relationship between HULC, Treg cells, and PD-1 was determined. The animals were divided into H22 hepatic carcinoma and S180 sarcoma groups. Each group was divided into Foxp3-/-C57BL/6J and C57BL/6J mice. Thereafter, mice were inoculated with 0.1 ml S180 sarcoma cells or 0.1 ml H22 hepatoma cells, at a concentration of 1 × 107/ml. The number of splenic CD4+CD25+Foxp3+ T cells was detected by flow cytometry, and serum interleukin-10 (IL-10) and transforming growth factor ß1 (TGF-ß1) levels were detected using a Luminex liquid suspension chip. Expression of PD-1, fork head box P3 (Foxp3), and HULC in the TME, were analyzed and the therapeutic effect of inhibiting the lncRNA HULC-Treg-PD-1 axis in malignant tumors was determined. Results: High expression of lncRNA HULC promotes the proliferation of Treg cells and increases PD-1 expression in the tumor microenvironment. The HULC-Treg-PD-1 axis plays an immunosuppressive role and promotes the proliferation of malignant tumors. Knocking out the Foxp3 gene can affect the HULC-Treg-PD-1 axis and reduce PD-1, IL-10, and TGF-ß1 expression to control the growth of malignant tumors. Conclusion: The lncRNA HULC-Treg-PD-1 axis promotes the growth of malignant tumors. This axis could be modulated to reduce PD-1, IL-10, and TGF-ß1 expression and the subsequent immune escape. The inhibition of immune escape in the tumor microenvironment can be achieved by controlling the LncRNA HULC-Treg-PD-1 axis.

Development and validation of a novel prognostic lncRNA signature based on the APOBEC3 family genes in gastric cancer.

Introduction: Gastric Cancer (GC) refers to a prevalent malignant cancer accompanied by a weak prognosis. The APOBEC3 family genes and lncRNAs are linked with cancer progression. Nevertheless, there is still a scarcity of data concerning the prognostic value of APOBEC3-related lncRNAs in GC. Methods: We extracted the data from GC samples, including transcriptome as well as clinical data, obtained from the TCGA database. Then, we screened for lncRNAs that were correlated with the APOBEC3 family genes and constructed an APOBEC3-related lncRNA prognostic signature (LPS) by utilizing univariate Cox and lasso regression analysis. Furthermore, we validated our constructed signature and evaluated it thoroughly, including analysis of its function, immunity, mutations, and clinical applications via multiple methods, including Metascape, GSEA, and analyses including TIC and TME, immune checkpoints, CNV and SNPs, Kaplan-Meier survival curves, nomogram, decision tree and drug prediction analysis. Finally, we overexpressed LINC01094 to evaluate the impacts on the proliferation as well as migration with regards to KATO-2 cells. Results: We selected eight lncRNAs for our APOBEC3-related LPS, which is demonstrated as a valuable tool in predicting the individual GC patients' prognosis. Subsequently, we segregated the samples into subgroups of high-as well as low-risk relying on the risk score with regards to APOBEC3-related LPS. By performing functional analysis, we have shown that immune-as well as tumor-related pathways were enriched in high- and low-risk GC patients. Furthermore, immune analysis revealed a robust correlation between the APOBEC3-related LPS and immunity. We found that immune checkpoints were significantly associated with the APOBEC3-related LPS and were greatly exhibited in GC tumor and high-risk samples. Mutational analysis suggested that the mutational rate was greater in low-risk samples. Furthermore, we predicted small molecular drugs displayed greater sensitivity in patients categorized as high-risk. Moreover, the immune response was also better in high-risk patients. Of these drugs, dasatinib was significant in both methods and might be considered a potential novel drug for treating high-risk GC patients. Finally, we found that LINC01094 has the potential to enhance the migration, proliferation as well as inhibit apoptosis of KATO-2 in GC cells. And Dasatinib has an inhibitory effect on the migration as well as proliferation in GC cells. Conclusion: We created a novel APOBEC3-related LPS in predicting the prognosis with regards to individual GC patients. Importantly, this APOBEC3-related LPS was closely associated with immunity and might guide clinical treatment.

Epitranscriptomic orchestrations: Unveiling the regulatory paradigm of m6A, A-to-I editing, and m5C in breast cancer via long noncoding RNAs and microRNAs.

Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC. Noncoding RNAs (ncRNAs), acting as posttranscriptional regulators, influence physiological and pathological processes, including cancer. RNA modifications in long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) add an extra layer to gene expression control. This review delves into recent insights into epitranscriptomic RNA modifications, such as N-6-methyladenosine (m6A), adenine-to-inosine (A-to-I) editing, and 5-methylcytosine (m5C), specifically in the context of lncRNA and miRNAs in BC, highlighting their potential implications in BC development and progression. Understanding this intricate regulatory landscape is vital for deciphering the molecular mechanisms underlying BC and identifying potential therapeutic targets.

Expression profiles and gene set enrichment analysis of the transcriptomes from the cancer tissue, white adipose tissue and paracancer tissue with colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide and is related to diet and obesity. Currently, crosstalk between lipid metabolism and CRC has been reported; however, the specific mechanism is not yet understood. In this study, we screened differentially expressed long non-coding RNAs (lncRNAs) and mRNAs from primary cancer, paracancer, and white adipose tissue of CRC patients. We screened and analyzed the genes differentially expressed between primary and paracancer tissue and between paracancer and white adipose tissue but not between primary and white adipose tissue. According to the results of the biological analysis, we speculated a lncRNA (MIR503HG) that may be involved in the crosstalk between CRC and lipid metabolism through exosome delivery. Methods: We screened differentially expressed long non-coding RNAs (lncRNAs) and mRNAs from primary cancer, paracancer, and white adipose tissue of CRC patients. We screened and analyzed the genes differentially expressed between primary and paracancer tissue and between paracancer and white adipose tissue but not between primary and white adipose tissue. Results: We speculated a lncRNA (MIR503HG) that may be involved in the crosstalk between CRC and lipid metabolism through exosome delivery. Conclusions: In this study, the findings raise the possibility of crosstalk between lipid metabolism and CRC through the exosomal delivery of lncRNAs.

LncRNA FRMD6-AS1/miR-491-5p/USP13 pathway attenuated ferroptosis and contributed to liver fibrosis.

Liver fibrosis is an invertible pathophysiologic process featured by excessive accumulation of extracellular matrix (ECM) which injures liver cells and activates hepatic stellate cells (HSCs). Besides, inducing ferroptosis in activated HSCs can alleviate liver fibrosis. LncRNAs modulate ferroptosis in activated HSCs and ECM deposition in liver fibrosis. However, the role of lncRNA FRMD6-AS1 in liver fibrosis is not discovered. In this study, lncRNA FRMD6-AS1 was dramatically up-regulated in activated HSCs. Knockdown of FRMD6-AS1 markedly increased iron ion, ROS and MDA levels, decreased GSH level, SLC7A11 and GPX4 protein expressions in activated HSCs. In addition, HSCs activation markers α-SMA and COL1α1 expressions were up-regulated in activated HSCs; knockdown of FRMD6-AS1 markedly down-regulated α-SMA and COL1α1 expressions in HSCs. Besides, lncRNA FRMD6-AS1 could interact with miR-491-5p, and negatively modulate miR-491-5p expression. USP13 was a target of miR-491-5p, and could be negatively modulated by miR-491-5p. Moreover, FRMD6-AS1 knockdown increased iron ion and ROS levels, decreased SLC7A11 and GPX4 protein expressions, facilitated HSCs viability, and up-regulated α-SMA and COL1α1 expressions via miR-491-5p/USP13 pathway. Finally, FRMD6-AS1 knockdown restored liver tissue structure and abrogated fibrosis in livers in a CCL4 liver fibrosis mouse model. Hence, lncRNA FRMD6-AS1/miR-491-5p/USP13 pathway repressed ferroptosis, promoted ECM deposition and facilitated liver fibrosis in vitro and in vivo models.

Identification of long noncoding RNAs downregulated specifically in ovarian high-grade serous carcinoma.

Purpose: To investigate whether long noncoding RNAs (lncRNAs) are involved in the development or malignant behavior of ovarian high-grade serous carcinoma (HGSC), we attempted to identify lncRNAs specific to HGSC. Methods: Total RNAs were isolated from HGSC, normal ovarian, and fallopian tube tissue samples and were subjected to a PCR array that can analyze 84 cancer-associated lncRNAs. The lncRNAs that were upregulated and downregulated in HGSC in comparison to multiple samples of normal ovary and fallopian tube were validated by real-time RT-PCR. To infer the function, ovarian cancer cell lines that overexpress the identified lncRNAs were established, and the activation of cell proliferation, migration, and invasion was analyzed. Results: Eleven lncRNAs (ACTA2-AS1, ADAMTS9-AS2, CBR3-AS1, HAND2-AS1, IPW, LINC00312, LINC00887, MEG3, NBR2, TSIX, and XIST) were downregulated in HGSC samples. We established the cell lines that overexpress ADAMTS9-AS2, CBR3-AS1, or NBR2. In cell lines overexpressing ADAMTS9-AS2, cell proliferation was suppressed, but migration and invasion were promoted. In cell lines overexpressing CBR3-AS1 or NBR2, cell migration tended to be promoted, although cell proliferation and invasion were unchanged. Conclusion: We identified eleven lncRNAs that were specifically downregulated in HGSC. Of these, CBR3-AS1, NBR2, and ADAMTS9-AS2 had unique functions in the malignant behaviors of HGSC.

The human infertility single-cell testis atlas (HISTA): an interactive molecular scRNA-Seq reference of the human testis.

BACKGROUND: Single-cell RNA-seq (scRNA-Seq) has been widely adopted to study gene expression of the human testis. Several datasets of scRNA-Seq from human testis have been generated from different groups processed with different informatics pipelines. An integrated atlas of scRNA-Seq expression constructed from multiple donors, developmental ages, and fertility states would be widely useful for the testis research community. OBJECTIVE: To describe the generation and use of the human infertility single-cell testis atlas (HISTA), an interactive web tool for understanding human spermatogenesis through scRNA-Seq analysis. METHODS: We obtained scRNA-Seq datasets derived from 12 donors, including healthy adult controls, juveniles, and several infertility cases, and reprocessed these data using methods to remove batch effects. Using Shiny, an open-source environment for data visualization, we created numerous interactive tools for exploring the data, some of which support simple statistical hypothesis testing. We used the resulting HISTA browser and its underlying data to demonstrate HISTA's value for testis researchers. RESULTS: A primary application of HISTA is to search by a single gene or a set of genes; thus, we present various analyses that quantify and visualize gene expression across the testis cells and pathology. HISTA also contains machine-learning-derived gene modules ("components") that capture the entire transcriptional landscape of the testis tissue. We show how the use of these components can simplify the highly complex data in HISTA and assist with the interpretation of genes with unknown functions. Finally, we demonstrate the diverse ways HISTA can be used for new data analysis, including hypothesis testing. DISCUSSION AND CONCLUSIONS: HISTA is a research environment that can help scientists organize and understand the high-dimensional transcriptional landscape of the human testis. HISTA has already contributed to published testis research and can be updated as needed with input from the research community or downloaded and modified for individual needs.

A long non-coding RNA functions as a competitive endogenous RNA to modulate TaNAC018 by acting as a decoy for tae-miR6206.

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.

LncRNA EBLN3P Accelerates Cell Proliferation and Invasion of Colon Cancer through Modulating the miR-519d-3p/ZFP91 Axis.

Purpose: The study aims to explore the roles and underlying mechanisms of long noncoding RNAs endogenous bornavirus-like nucleoprotein (lncRNA EBLN3P) in colon cancer, emphasizing the potential impact of these insights on advancing colon cancer treatment strategies. By shedding light on lncRNA EBLN3P's involvement, this research could contribute to the development of novel therapeutic approaches, enhancing the efficacy of interventions for colon cancer patients. Methods: We employed quantitative reverse transcription polymerase chain reaction to assess the levels of lncRNA EBLN3P, zinc finger protein (ZFP91), and miR-519d-3p, alongside CCK-8 and EdU assays for cell proliferation, flow cytometry for apoptosis, and Transwell and wound healing assays for migration and invasion. The in vivo function of lncRNA EBLN3P was investigated through a xenograft model, and protein levels were evaluated via Western blot analysis. Results: LncRNA EBLN3P was found to be upregulated in colon cancer tissues and cells, promoting cell proliferation and metastasis while inhibiting apoptosis. Downregulation of lncRNA EBLN3P reduced tumor size, volume, and weight in a mouse model. MiR-519d-3p, which negatively interacts with lncRNA EBLN3P, was found to be downregulated in colon cancer tissues and cell lines. Its upregulation hindered cancer cell proliferation and metastasis while enhancing apoptosis. ZFP91, a binding partner of miR-519d-3p, was upregulated in colon cancer and inversely related to miR-519d-3p levels. Rescue experiments indicated that the effects of lncRNA EBLN3P silencing could be reversed by miR-519d-3p suppression, but were mitigated by ZFP91 downregulation. Conclusion: LncRNA EBLN3P facilitates colon cancer progression via the miR-519d-3p/ZFP91 axis, presenting a novel understanding of lncRNA EBLN3P's role and offering potential therapeutic insights for colon cancer treatment. This study fills a critical gap by linking lncRNA EBLN3P with the miR-519d-3p/ZFP91 axis in the context of colon cancer, thereby broadening our understanding of the molecular mechanisms underlying colon cancer progression.

LncRNA XIST modulates miR-328-3p ectopic expression in lung injury induced by tobacco-specific lung carcinogen NNK both in vitro and in vivo.

BACKGROUND AND PURPOSE: It is well acknowledged that tobacco-derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco-derived carcinogen nicotine-derived nitrosamine ketone (NNK)-treated A/J mice. EXPERIMENTAL APPROACH: RNA sequencing was used to detect the level of long non-coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR-328-3p in vitro, and NNK-treated A/J mice were used to test their function in vivo. In vivo levels of miR-328-3p and lncRNA XIST were analysed, using in situ hybridization. miR-328-3p agomir and lncRNA XIST-specific siRNA were used to manipulate in vivo levels of miR-328-3p and lncRNA XIST in A/J mice. KEY RESULTS: LncRNA XIST was up-regulated in NNK-induced lung injury and dominated the NNK-induced ectopic miRNA expression in NNK-induced lung injury both in vitro and in vivo. Either lncRNA XIST silencing or miR-328-3p overexpression exerted opposing effects in lung normal and cancer cells regarding cell migration. LncRNA XIST down-regulated miR-328-3p levels as a miRNA sponge, and miR-328-3p targeted the 3'-UTR of FZD7 mRNA, which is ectopically overexpressed in lung cancer patients. Both in vivo lncRNA XIST silencing and miR-328 overexpression could rescue NNK-induced lung injury and aberrant overexpression of the lung cancer biomarker CK19 in NNK-treated A/J mice. CONCLUSIONS AND IMPLICATIONS: Our results highlight the promotive effect of lncRNA XIST in NNK-induced lung injury and elucidate its post-transcriptional mechanisms, indicating that targeting lncRNA XIST/miR-328-3p could be a potential therapeutic strategy to prevent tobacco carcinogen-induced lung injury in vivo.

Prediction of LncRNA-protein Interactions Using Auto-Encoder, SE-ResNet Models and Transfer Learning.

BACKGROUND: Long non-coding RNA (lncRNA) plays a crucial role in various biolog-ical processes, and mutations or imbalances of lncRNAs can lead to several diseases, including cancer, Prader-Willi syndrome, autism, Alzheimer's disease, cartilage-hair hypoplasia, and hear-ing loss. Understanding lncRNA-protein interactions (LPIs) is vital for elucidating basic cellular processes, human diseases, viral replication, transcription, and plant pathogen resistance. Despite the development of several LPI calculation methods, predicting LPI remains challenging, with the selection of variables and deep learning structure being the focus of LPI research. METHODS: We propose a deep learning framework called AR-LPI, which extracts sequence and secondary structure features of proteins and lncRNAs. The framework utilizes an auto-encoder for feature extraction and employs SE-ResNet for prediction. Additionally, we apply transfer learning to the deep neural network SE-ResNet for predicting small-sample datasets. RESULTS: Through comprehensive experimental comparison, we demonstrate that the AR-LPI ar-chitecture performs better in LPI prediction. Specifically, the accuracy of AR-LPI increases by 2.86% to 94.52%, while the F-value of AR-LPI increases by 2.71% to 94.73%. CONCLUSION: Our experimental results show that the overall performance of AR-LPI is better than that of other LPI prediction tools.

Understanding the Roles of Non-coding RNAs and Exosomal Non-Coding RNAs in Diabetic Nephropathy.

One of the greatest serious side effects of diabetes is diabetic nephropathy (DN), which is also the key factor in the sometimes-deadly diabetic end-stage renal disease. Progressive renal interstitial fibrosis is closely associated with oxidative stress, and the extracellular matrix is typically a feature of DN. Some RNAs formed by genome transcription that are not translated into proteins are recognized as noncoding RNAs. It has been shown that ncRNAs control apoptosis, inflammatory response, cell proliferation, autophagy, and other pathogenic processes, contributing to the pathogenesis of DN. Exosomes are nano-carriers vesicles that variety in size from 40 to 160 nm. Exosomes are widely present and dispersed in different bodily fluids, plentiful in nucleic acids, lipids, and proteins (microRNA, mRNA, tRNA, lncRNA, circRNA, etc.). Exosomes play a crucial role as messengers for cellular communication. They transport and transmit key signaling molecules, participate in the transfer of information and materials between cells, control cellular physiological processes, and are carefully linked to the beginning and development of many diseases. Herein, we summarized the role of different ncRNAs in DN. Moreover, we highlighted the role of the exosomal form of ncRNAs in the DN pathogenesis.

Profiling of long non-coding RNAs in hippocampal-entorhinal system subfields: impact of RN7SL1 on neuroimmune response modulation in Alzheimer's disease.

Alzheimer's disease (AD) is recognized as the predominant cause of dementia, and neuroimmune processes play a pivotal role in its pathological progression. The involvement of long non-coding RNAs (lncRNAs) in AD has attracted widespread attention. Herein, transcriptomic analysis of 262 unique samples extracted from five hippocampal-entorhinal system subfields of individuals with AD pathology and without AD pathology revealed distinctive lncRNA expression profiles. Through differential expression and coexpression analyses, we identified 16 pivotal lncRNAs. Notably, RN7SL1 knockdown significantly modulated microglial responses upon oligomeric amyloid-ß stimulation, resulting in a considerable decrease in proinflammatory cytokine production and subsequent neuronal damage. These findings highlight RN7SL1 as an essential neuroimmune-related lncRNA that could serve as a prospective target for AD diagnosis and treatment.

Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening.

Background: The disulfide stress-induced cell death known as disulfidptosis is characterized by the disintegration of cytoskeletal proteins and F-actin as a result of an excessive buildup of disulfides within the cell. The relationship between disulfidptosis-associated long non-coding RNA (lncRNA) in hepatocellular carcinoma (HCC) progression is still not clearly understood. In this article, we aim to explore the crucial role of lncRNA in HCC. Methods: We initially obtained lncRNA related to HCC and clinical data from TCGA. The genes associated with disulfidptosis were identified through co-expression analysis, Cox regression, and Lasso regression. Additionally, we established a prognostic model for verification. Results: The risk model constructed with disulfidptosis-related lncRNA has been confirmed to be a good predictor of high and low-risk groups of HCC patients through survival curves, independent prognostic analysis, concordance index (C-index), ROC curves, and Kaplan-Meier plots. We also discovered differences in the response to immune targets and anticancer drugs between the two groups of patients, with GDC0810, Osimertinib, Paclitaxel, and YK-4-279 being more effective for patients in the high-risk group. Conclusion: In conclusion, we have developed a risk model that can guide future efforts to diagnose and treat HCC.

LncRNA HOXA­AS2 is a prognostic and clinicopathological predictor in patients with cancer: A meta­analysis.

Elevated expression of long non-coding RNA homeobox A cluster antisense RNA 2 (lncRNA HOXA-AS2) is known to have prognostic value in various solid tumors. The present meta-analysis aimed to comprehensively quantify its prognostic significance across a wider spectrum of malignancies and to provide an updated synthesis of evidence that could refine prognostic models. To achieve this aim, multiple databases were carefully searched for lncRNA HOXA-AS2-related articles published in the past 10 years. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to demonstrate the prognostic value of lncRNA HOXA-AS2 using Stata 15.0 software. The function of lncRNA HOXA-AS2 was inferred from its associations with key clinical outcomes such as lymph node metastasis, distant metastasis, tumor stage and tumor size, which may reflect its role in tumor biology. In the present systematic review and meta-analysis of 454 patients across 7 studies, it was found that high lncRNA HOXA-AS2 expression was significantly associated with a shorter overall survival (OS) time in patients with cancer (HR=2.14; 95% CI, 1.40-3.27; P<0.001). High lncRNA HOXA-AS2 expression was also associated with lymph node metastasis [odds ratio (OR)=2.06; 95% CI, 1.07-3.99; P=0.032], distant metastasis (OR=2.11; 95% CI, 1.15-3.88; P=0.016), advanced tumor stage (OR=2.71; 95% CI, 1.50-4.89; P=0.001) and larger tumor size (OR=2.02; 95% CI, 0.86-4.78; P=0.006). However, no significant association was observed with age (OR=1.00; 95% CI, 0.63-1.59; P=0.991) or sex (OR=1.55; 95% CI, 0.72-3.34; P=0.258). In conclusion, elevated expression of lncRNA HOXA-AS2 was significantly related to poor clinical outcomes in various cancer types, such as osteosarcoma, non-small cell lung cancer and papillary thyroid carcinoma, a finding that was further confirmed by the present study. Specifically, the potential of lncRNAHOXA-AS2 as a biomarker in assessing tumor stage, metastasis risk and OS in patients was demonstrated. However, the results of the present study also indicated that the expression of lncRNA HOXA-AS2 was not significantly associated with age or sex, suggesting its role in cancer progression might be independent of these factors. This insight may direct future research to place more focus on the relationship between lncRNA HOXA-AS2 and specific cancer types and clinical characteristics.

Identification of m6A/m5C-related lncRNA signature for prediction of prognosis and immunotherapy efficacy in esophageal squamous cell carcinoma.

N6-methyladenosine (m6A) and 5-methylcytosine (m5C) RNA modifications have garnered significant attention in the field of epigenetic research due to their close association with human cancers. This study we focus on elucidating the expression patterns of m6A/m5C-related long non-coding RNAs (lncRNAs) in esophageal squamous cell carcinoma (ESCC) and assessing their prognostic significance and therapeutic potential. Transcriptomic profiles of ESCC were derived from public resources. m6A/m5C-related lncRNAs were obtained from TCGA using Spearman's correlations analysis. The m6A/m5C-lncRNAs prognostic signature was selected to construct a RiskScore model for survival prediction, and their correlation with the immune microenvironment and immunotherapy response was analyzed. A total of 606 m6A/m5C-lncRNAs were screened, and ESCC cases in the TCGA cohort were stratified into three clusters, which showed significantly distinct in various clinical features and immune landscapes. A RiskScore model comprising ten m6A/m5C-lncRNAs prognostic signature were constructed and displayed good independent prediction ability in validation datasets. Patients in the low-RiskScore group had a better prognosis, a higher abundance of immune cells (CD4 + T cell, CD4 + naive T cell, class-switched memory B cell, and Treg), and enhanced expression of most immune checkpoint genes. Importantly, patients with low-RiskScore were more cline benefit from immune checkpoint inhibitor treatment (P < 0.05). Our findings underscore the potential of RiskScore system comprising ten m6A/m5C-related lncRNAs as effective biomarkers for predicting survival outcomes, characterizing the immune landscape, and assessing response to immunotherapy in ESCC.

Role of LncRNA H19 in tumor progression and treatment.

As one of the earliest discovered lncRNA molecules, lncRNA H19 is usually expressed in large quantities during embryonic development and is involved in cell differentiation and tissue formation. In recent years, the role of lncRNA H19 in tumors has been gradually recognized. Increasing evidence suggests that its aberrant expression is closely related to cancer development. LncRNA H19 as an oncogene not only promotes the growth, proliferation, invasion and metastasis of many tumors, but also develops resistance to treatment, affecting patients' prognosis and survival. Therefore, in this review, we summarise the extensive research on the involvement of lncRNA H19 in tumor progression and discuss how lncRNA H19, as a key target gene, affects tumor sensitivity to radiotherapy, chemotherapy and immunotherapy by participating in multiple cellular processes and regulating multiple signaling pathways, which provides a promising prospect for further research into the treatment of cancer.