Antisense RNA Research Articles

Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma

Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patients diagnosed with LUAD and 60 healthy volunteers at The First Affiliated Hospital of Huzhou University from April, 2023 to December, 2023 were enrolled in the present study. A LRHGs model was established using least absolute shrinkage and selection operator analyses of The Cancer Genome Atlas-LUAD datasets. The underlying mechanisms of the LRHGs were investigated via Gene Set Enrichment Analysis and Gene Set Variation Analysis. Additionally, the diagnostic role of serum HOXD cluster antisense RNA 2 (HOXD-AS2) was assessed by receiver operating characteristic (ROC) curve analysis. Lastly, TCGA-LUAD samples were divided into high- and low-HOXD-AS2 expression groups based on the median expression. The associations between HOXD-AS2 expression and miR-4538 as well as Calmodulin-Dependent Protein Kinase Type II subunit Beta (CAMK2B) levels were conducted through Pearson correlation analysis. A comprehensive analysis identified 141 differentially expressed lncRNAs between 539 LUAD tissues and 59 normal samples. A prognostic marker for overall survival was established by constructing a predictive signature consisting of 9 LRHGs. Subsequently, 474 LUAD samples were categorized into a high or low-risk group based on the median of the risk score. An independent prognostic model was constructed to confirm the validity of this categorization. Further comparisons of the clinicopathological features and LRHG-related pathways were performed between the two groups. Examinations of LRHG expression in two LUAD clusters and of the association between LRHG expression and immune infiltration were also conducted. HOXD-AS2 expression was shown to be elevated in LUAD tissues compared with matched normal tissues, and the serum HOXD-AS2 level was also notably increased in LUAD samples compared with healthy controls. The results of the ROC analysis indicated that the sensitivity and specificity of HOXD-AS2 were higher than that of cytokeratin-19 fragment (CYFRA21-1), which is a serum marker for LUAD. Pearson analyses indicated that miR-4538 level was negatively associated with HOXD-AS2 expression, but CAMK2B level showed positive correlation in LUAD. The results of the present study therefore indicated that the constructed LRHG model, particularly HOXD-AS2, could independently diagnose and predict the prognosis of LUAD, which suggested the underlying mechanism of the HOXD-AS2/miR-4538/CAMK2B, and might offer efficient strategies for LUAD treatment.

ROR1-AS1: A Meaningful Long Noncoding RNA in Oncogenesis.

Long noncoding RNA (lncRNA) is a non-coding RNA with a length of more than 200 nucleotides, involved in multiple regulatory processes in vivo, and is related to the physiology and pathology of human diseases. An increasing number of experimental results suggest that when lncRNA is abnormally expressed, it results in the development of tumors. LncRNAs can be divided into five broad categories: sense, antisense, bidirectional, intronic, and intergenic. Studies have found that some antisense lncRNAs are involved in a variety of human tumorigenesis. The newly identified ROR1-AS1, which functions as an antisense RNA of ROR1, is located in the 1p31.3 region of the human genome. Recent studies have reported that abnormal expression of lncRNA ROR1-AS1 can affect cell growth, proliferation, invasion, and metastasis and increase oncogenesis and tumor spread, indicating lncRNA ROR1-AS1 as a promising target for many tumor biological therapies. In this study, the pathophysiology and molecular mechanism of ROR1-AS1 in various malignancies are discussed by retrieving the related literature. ROR1-AS1 is a cancer-associated lncRNA, and studies have found that it is either over- or underexpressed in multiple malignancies, including liver cancer, colon cancer, osteosarcoma, glioma, cervical cancer, bladder cancer, lung adenocarcinoma, and mantle cell lymphoma. Furthermore, it has been demonstrated that lncRNA ROR1-AS1 participates in proliferation, migration, invasion, and suppression of apoptosis of cancer cells. Furthermore, lncRNA ROR1-AS1 promotes the development of tumors by up-regulating or downregulating ROR1-AS1 conjugates and various pathways and miR-504, miR-4686, miR-670-3p, and miR-375 sponges, etc., suggesting that lncRNA ROR1-AS1 may be used as a marker in tumors or a potential therapeutic target for a variety of tumors.

Mechanism of HOXA10 in nasopharyngeal carcinoma cell proliferation through the PTPRG-AS1/USP1 axis.

Nasopharyngeal carcinoma (NPC) is an epithelial carcinoma arising from the nasopharyngeal mucosal lining. The present study sought to analyze the mechanism by which homeobox A10 (HOXA10) affects NPC cell proliferation. The expression levels of HOXA10/long noncoding RNA (lncRNA) PTPRG antisense RNA 1 (PTPRG-AS1)/ubiquitin-specific peptidase 1 (USP1) in NPC tissues and cells were determined. Cell proliferation was evaluated. The enrichment of HOXA10 on the PTPRG-AS1 promoter was determined. The binding of PTPRG-AS1, HuR, and USP1 to each other was analyzed via RNA immunoprecipitation. USP1 mRNA stability was determined after actinomycin D treatment. The role of the PTPRG-AS1/USP1 axis in NPC cell proliferation was analyzed in combined experiments. The role of HOXA10 in vivo was confirmed in xenograft tumor models. The results revealed that HOXA10 was overexpressed in NPC. HOXA10 downregulation reduced NPC cell proliferation. PTPRG-AS1 and USP1 were upregulated in NPC. HOXA10 bound to the PTPRG-AS1 promoter to increase PTPRG-AS1 expression, and the binding of PTPRG-AS1 to HuR increased USP1 expression. PTPRG-AS1 or USP1 overexpression attenuated the inhibitory effects of HOXA10 downregulation on NPC cell proliferation. HOXA10 downregulation inhibited in vivo NPC proliferation through the PTPRG-AS1/USP1 axis. In conclusion, HOXA10 facilitates NPC cell proliferation in vitro and in vivo through the PTPRG-AS1/USP1 axis.

LNX1-AS2 as a Key Prognostic and Immunotherapy Response Biomarker for Lung Adenocarcinoma.

The role of LNX1 antisense RNA 2 (LNX1-AS2) in lung adenocarcinoma (LUAD) remains unclear. This study aimed to investigate the association between LNX1-AS2 and LUAD by employing bioinformatics analysis and experimental validation. Statistical analysis and database interrogation were utilized to assess correlations among LNX1-AS2 expression, clinical characteristics of LUAD patients, prognostic factors, regulatory networks, and immune infiltration. LNX1-AS2 expression in LUAD cell lines was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). The study found significantly elevated levels of LNX1-AS2 expression in patients with LUAD. Furthermore, elevated LNX1-AS2 expression in LUAD patients did not significantly correlate with gender (p = 0.041) or race (p = 0.049). Importantly, high LNX1-AS2 expression levels were associated with poorer overall survival (OS, p = 0.042) and disease-specific survival (DSS, p = 0.040) in LUAD patients. Additionally, high LNX1-AS2 expression (p = 0.015) was independently correlated with OS in LUAD patients. The phenotype characterized by high LNX1-AS2 expression was also found to be enriched for asthma, allograft rejection, drug metabolism cytochrome P450, metabolism of xenobiotics by cytochrome P450, olfactory transduction, renin-angiotensin system, retinol metabolism, pentose and glucuronate interconversions, and porphyrin and chlorophyll metabolism. A significant correlation was identified between the expression levels of LNX1-AS2 and immune infiltration in the context of LUAD. Elevated expression of LNX1-AS2 was notably detected in LUAD cell lines as opposed to Beas-2B. A noteworthy relationship was established among increased LNX1-AS2 expression in LUAD patients, unfavorable prognosis, and heightened immune infiltration. These findings suggest that the LNX1-AS2 gene could serve as a valuable prognostic indicator for LUAD and a potential predictor of response to immunotherapy.

High expression of LncRNA HOTAIR is a risk factor for temozolomide resistance in glioblastoma via activation of the miR-214/β-catenin/MGMT pathway

HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. However, the mechanisms underlying HOTAIR-mediated TMZ resistance remains poorly understood. HOTAIR expression in glioma-related public datasets and drug response estimation were analyzed using bioinformatics. These findings were verified by overexpressing HOTAIR in TMZ-sensitive U251 cells and/or silencing HOTAIR in resistant U251 cells (U251R). The cytotoxic effects were evaluated using cell viability assay and flow cytometry analysis of cell cycle and apoptosis. In this study, we found that HOTAIR was upregulated in TMZ-resistant GBM cell lines and patients with high HOTAIR expression responded poorly to TMZ therapy. HOTAIR knockdown restored TMZ sensitivity in U251R cells, while HOTAIR overexpression conferred TMZ resistance in U251 cells. Wnt/β-catenin signaling was enriched in patients with high HOTAIR expression; consistently, HOTAIR positively regulated β-catenin expression in U251 cells. Moreover, HOTAIR-mediated TMZ resistance was associated with increased MGMT protein level, which resulted from the HOTAIR/miR-214-3p/β-catenin network. Besides, GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin. Thus, we conlcude that HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.

LncRNA BRE-AS1 regulates the JAK2/STAT3-mediated inflammatory activation via the miR-30b-5p/SOC3 axis in THP-1 cells

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in numerous biological processes, including macrophage-mediated inflammatory responses, which play a critical role in the progress of diverse diseases. This study focuses on the regulatory function of lncRNA brain and reproductive organ-expressed protein (BRE) antisense RNA 1 (BRE-AS1) in modulating the inflammatory activation of monocytes/macrophages. Employing the THP-1 cell line as a model, we demonstrate that lipopolysaccharide (LPS) treatment significantly upregulates BRE-AS1 expression. Notably, specific knockdown of BRE-AS1 via siRNA transfection enhances LPS-induced expression of interleukin (IL)-6 and IL-1β, while not affecting tumor necrosis factor (TNF)-α levels. This selective augmentation of pro-inflammatory cytokine production coincides with increased phosphorylation of Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3. Furthermore, BRE-AS1 suppression results in the downregulation of suppressor of cytokine signaling (SOCS)3, an established inhibitor of the JAK2/STAT3 pathway. Bioinformatics analysis identified binding sites for miR-30b-5p on both BRE-AS1 and SOCS3 mRNA. Intervention with a miR-30b-5p inhibitor and a synthetic RNA fragment that represents the miR-30b-5p binding site on BRE-AS1 attenuates the pro-inflammatory effects of BRE-AS1 knockdown. Conversely, a miR-30b-5p mimic replicated the BRE-AS1 attenuation outcomes. Our findings elucidate the role of lncRNA BRE-AS1 in modulating inflammatory activation in THP-1 cells via the miR-30b-5p/SOCS3/JAK2/STAT3 signaling pathway, proposing that manipulation of macrophage BRE-AS1 activity may offer a novel therapeutic avenue in diseases characterized by macrophage-driven pathogenesis.

TGIRT-seq of Inflammatory Breast Cancer Tumor and Blood Samples Reveals Widespread Enhanced Transcription Impacting RNA Splicing and Intronic RNAs in Plasma.

Inflammatory breast cancer (IBC) is the most aggressive and lethal breast cancer subtype but lacks unequivocal genomic differences or robust biomarkers that differentiate it from non-IBC. Here, Thermostable Group II intron Reverse Transcriptase RNA-sequencing (TGIRT-seq) revealed myriad differences in tumor samples, Peripheral Blood Mononuclear Cells (PBMCs), and plasma that distinguished IBC from non-IBC patients and healthy donors across all tested receptor-based subtypes. These included numerous differentially expressed protein-coding gene and non-coding RNAs in all three sample types, a granulocytic immune response in IBC PBMCs, and over- expression of antisense RNAs, suggesting wide-spread enhanced transcription in both IBC tumors and PBMCs. By using TGIRT-seq to quantitate Intron-exon Depth Ratios (IDRs) and mapping reads to both genome and transcriptome reference sequences, we developed methods for parallel analysis of transcriptional and post-transcriptional gene regulation. This analysis identified numerous differentially and non-differentially expressed protein-coding genes in IBC tumors and PBMCs with high IDRs, the latter reflecting rate-limiting RNA splicing that negatively impacts mRNA production. Mirroring gene expression differences in tumors and PBMCs, over-represented protein-coding gene RNAs in IBC patient plasma were largely intronic RNAs, while those in non- IBC patients and healthy donor plasma were largely mRNA fragments. Potential IBC biomarkers in plasma included T-cell receptor pre-mRNAs and intronic, LINE-1, and antisense RNAs. Our findings provide new insights into IBC and set the stage for monitoring disease progression and response to treatment by liquid biopsy. The methods developed for parallel transcriptional and post- transcriptional gene regulation analysis have potentially broad RNA-seq and clinical applications.

GRK2 Protein Mediates the ANRIL, a lncRNA, to Affect the Proliferation and Apoptosis of Kasumi-1 Cells.

A long non-coding RNAs (LncRNAs) called antisense noncoding RNA in the INK4 locus (ANRIL), has emerged as substantial regulators of cell survival in acute myeloid leukemia (AML). However, its speciffc and potential mechanism is uncertain in AML. In this research, we investigated the role of ANRIL in cell proliferation, apoptosis, and the underlying mechanism in AML cells. ANRIL expression was quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Kasumi-1 cells were transfected with LV-ANRIL plasmid to upregulate ANRIL expression, with or without co-transfection with a G Protein-Coupled Receptor Kinase 2 (GRK2) siRNA. Additionally, these cells were transfected with sh-ANRIL plasmid to inhibit ANRIL expression, with or without co-transfection with a GRK2 overexpression plasmid. Cell proliferation and apoptosis were determined using the cell counting kit-8 (CCK8) and flow cytometry. Protein expression levels of phosphatidylinositide 3-kinases (PI3K), protein kinase B (AKT), phosphorylated-Akt (p-AKT), Bcl-2-associated protein x (BAX), B-cell leukemia/lymphoma 2 protein (BCL-2), proliferating cell nuclear antigen (PCNA), cleaved caspase-3, and GRK2 were detected by western blot. The RNA-binding protein immunoprecipitation (RIP) assay was conducted to investigate the interaction between ANRIL and GRK2. ANRIL expression was increased in Kasumi-1 cells. ANRIL upregulation expression promoted cell proliferation and inhibited apoptosis. Furthermore, its upregulation led to increased expressions of PI3K, AKT, p-AKT, PCNA, and BCL-2, and decreased expression of BAX in Kasumi-1 cells. Additionally, transfection with GRK2 siRNA attenuated the promoting effect of LV-ANRIL on Kasumi-1 cells proliferation and the PI3K/AKT pathway, increased BAX and cleaved caspase-3 expressions, and decreased BCL-2 and PCNA expressions. GRK2 overexpression reversed the inhibitory effect of sh-ANRIL on cell proliferation and the PI3K/AKT pathway. Furthermore, it promoted BCL-2 and PCNA expressions, and inhibited BAX and cleaved caspase-3 expressions. RIP assay confirmed the physical interaction between ANRIL and GRK2. The GRK2 protein-mediated ANRIL, increasing Kasumi-1 cell proliferation and inhibiting apoptosis by activating the PI3K/AKT/BCL-2 pathway.

Hereditary Transthyretin Amyloidosis Polyneuropathy.

In the last decade, we have witnessed dramatic improvements in the diagnosis, workup, management, and monitoring of patients with hereditary transthyretin amyloidosis (ATTRv). Updated imaging techniques (e.g., 99mTc-PYP scan) are increasingly being used in place of tissue biopsies for confirmation of disease. Novel treatments now include antisense oligonucleotide and RNA interference drugs, whereas new applications such as CRISPR and amyloid antibodies are being studied for potential use in the future. These treatments have dramatically improved quality of life and increased survival in patients with ATTRv. Despite these breakthroughs, many challenges remain. Some of these challenges include early recognition and diagnosis of ATTRv, monitoring and initiation of treatment in asymptomatic or paucisymptomatic carriers, adequate treatment in people with mixed phenotype (i.e., cardiac and neurological), and the emergence of new phenotypes in people living longer with the disease (i.e., central nervous system and ocular complications). Research in those areas of deficit is ongoing, and in the future, we may have preventive therapies, better biomarkers, more efficient therapies for organs that we cannot currently target, and enhanced diagnostic techniques with the help of novel imaging techniques and artificial intelligence. In this review, we will summarize the current knowledge about polyneuropathy related to ATTRv and its management, discuss methods to improve early diagnosis and monitoring, and discuss emerging trends.

Long noncoding RNA DDX11-AS1 represses sorafenib-induced ferroptosis in hepatocellular carcinoma cells via Nrf2-Keap1 pathway

Sorafenib, a first-line therapeutic option for advanced hepatocellular carcinoma (HCC), faces a formidable challenge in the form of emerging resistance. Recently, the oncogene DDX11 antisense RNA 1 (DDX11-AS1) has been implicated in various cancers, including HCC. However, its role in sorafenib resistance remains unknown. Our findings reveal that DDX11-AS1 is upregulated in sorafenib-resistant HCC cells, contributing to their resistance by suppressing ferroptosis. Further investigation elucidated the mechanism by which DDX11-AS1 activates the antioxidant Nrf2-Keap1 pathway. By interacting with Nrf2 and hindering its association with Keap1, DDX11-AS1 enhances the stability and nuclear translocation of Nrf2. In summary, our study unveils the potent role of DDX11-AS1 as an enhancer of sorafenib resistance, inhibiting sorafenib-induced ferroptosis through the activation of the Nrf2-Keap1 pathway in HCC. These findings offer a promising therapeutic strategy to overcome resistance and effectively treat HCC.

Serum lncRNA ITGB2-AS1 and ICAM-1 as novel biomarkers for rheumatoid arthritis and osteoarthritis diagnosis.

The complete circulating long non-coding RNAs (lncRNAs) signature of rheumatoid arthritis (RA) and osteoarthritis (OA) is still uncovered. The lncRNA integrin subunit beta 2 (ITGB2)-anti-sense RNA 1 (ITGB2-AS1) affects ITGB2 expression; however, there is a gap in knowledge regarding its expression and clinical usefulness in RA and OA. This study investigated the potential of serum ITGB2-AS1 as a novel diagnostic biomarker and its correlation with ITGB2 expression and its ligand intercellular adhesion molecule-1 (ICAM-1), disease activity, and severity in RA and primary knee OA patients. Forty-three RA patients, 35 knee OA patients, and 22 healthy volunteers were included. Compared with healthy controls, serum ITGB2-AS1 expression was upregulated in RA patients but wasn't significantly altered in knee OA patients, whereas serum ICAM-1 protein levels were elevated in both diseases. ITGB2-AS1 showed discriminative potential for RA versus controls (AUC = 0.772), while ICAM-1 displayed diagnostic potential for both RA and knee OA versus controls (AUC = 0.804, 0.914, respectively) in receiver-operating characteristic analysis. In the multivariate analysis, serum ITGB2-AS1 and ICAM-1 were associated with the risk of developing RA, while only ICAM-1 was associated with the risk of developing knee OA. A panel combining ITGB2-AS1 and ICAM-1 showed profound diagnostic power for RA (AUC = 0.9, sensitivity = 86.05%, and specificity = 91.67%). Interestingly, serum ITGB2-AS1 positively correlated with disease activity (DAS28) in RA patients and with ITGB2 mRNA expression in both diseases, while ICAM-1 positively correlated with ITGB2 expression in knee OA patients. Our study portrays serum ITGB2-AS1 as a novel potential diagnostic biomarker of RA that correlates with disease activity. A predictive panel combining ITGB2-AS1 and ICAM-1 could have clinical utility in RA diagnosis. We also spotlight the association of ICAM-1 with knee OA diagnosis. The correlation of serum ITGB2-AS1 with ITGB2 expression in both diseases may be insightful for further mechanistic studies.

Association of ANRIL Gene Polymorphisms with Gastric Cancer Risk: A Case-Control Study.

Background: Gastric cancer's (GC) cause is unknown, but its complexity indicates that, in addition to environmental factors, it may have genetic origins. Scientists are studying single-nucleotide polymorphisms (SNPs) in the antisense noncoding RNA in the INK4 locus (ANRIL) gene, which encodes a long noncoding RNA molecule. They found a link between the ANRIL gene product and some polymorphisms and GC, suggesting genetic changes may lead to precancerous conditions. Methods: In a case-control research that included 250 patients with GC and 210 controls who were age- and gender-matched, four SNPs within the ANRIL gene were genotyped. These SNPs were rs1333049, rs496892, rs2383207, and rs2151280. Tetra-primer amplification refractory mutation system-PCR was utilized to carry out the process of genotyping. Results: It was found that the chance of developing GC was connected with three SNPs rs2151280, rs1333049, and rs496892. Nevertheless, rs2383207 did not demonstrate any meaningful connection. In addition, whereas CCTC and TTCC haplotypes were shown to be less common, certain haplotypes that contained these SNPs (TTCG, TCTC, and TTTC) displayed a considerably higher prevalence in the cancer group in comparison to the control group. Conclusion: This study showed novel associations between specific ANRIL gene polymorphisms (SNPs) and the risk of GC. These findings shed light on the potential role of ANRIL SNPs in GC risk and highlight the need for additional research to clarify the underlying functional processes. Understanding these functional processes might lead to developing novel diagnostic or treatment approaches for this cancer.

Pathological R-loops in bacteria from engineered expression of endogenous antisense RNAs whose synthesis is ordinarily terminated by Rho.

In many bacteria, the essential factors Rho and NusG mediate termination of synthesis of nascent transcripts (including antisense RNAs) that are not being simultaneously translated. It has been proposed that in Rho's absence toxic RNA-DNA hybrids (R-loops) may be generated from nascent untranslated transcripts, and genome-wide mapping studies in Escherichia coli have identified putative loci of R-loop formation from more than 100 endogenous antisense transcripts that are synthesized only in a Rho-deficient strain. Here we provide evidence that engineered expression in wild-type E. coli of several such individual antisense regions on a plasmid or the chromosome generates R-loops that, in an RNase H-modulated manner, serve to disrupt genome integrity. Rho inhibition was associated with increased prevalence of antisense R-loops also in Xanthomonas oryzae pv. oryzae and Caulobacter crescentus. Our results confirm the essential role of Rho in several bacterial genera for prevention of toxic R-loops from pervasive yet cryptic endogenous antisense transcripts. Engineered antisense R-looped regions may be useful for studies on both site-specific impediments to bacterial chromosomal replication and the mechanisms of their resolution.

Diagnostic Value of Plasma Long Non-coding SLC26A4 Antisense RNA 1 Combined with Magnetic Resonance Imaging in Rectal Cancer

Diagnostic Value of Plasma Long Non-coding SLC26A4 Antisense RNA 1 Combined with Magnetic Resonance Imaging in Rectal Cancer

Development of biomarker signatures associated with anoikis to predict prognosis in patients with esophageal cancer: An observational study.

Anoikis, a form of programmed cell death linked to cancer, has garnered significant research attention. Esophageal cancer (ESCA) ranks among the most prevalent malignant tumors and represents a major global health concern. To ascertain whether anoikis-related genes (ARGs) can accurately predict ESCA prognosis, we evaluated the predictive value and molecular mechanisms of ARGs in ESCA and constructed an optimal model for prognostic prediction. Using the Cancer Genome Atlas (TCGA)-ESCA database, we identified ARGs with differences in ESCA. ARG signatures were generated using Cox regression. A predictive nomogram model was developed to forecast ARG signatures and patient outcomes in ESCA. Gene set enrichment analysis (GSEA) was employed to uncover potential biological pathways associated with ARG signatures. Estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) and cell-type identification by estimating relative subsets of RNA transcripts analyses were used to assess differences in the immune microenvironment of the ARG signature model. Based on ARGs, the patients with ESCA were divided into high and low groups, and the sensitivity of patients to drugs in the database of genomics of drug sensitivity in cancer was analyzed. Finally, the correlation between drug sensitivity and risk score was then evaluated based on the ARG signatures. Prognostic relevance was significantly linked to the ARG profiles of 5 genes: MYB binding protein 1a (MYBBP1A), plasminogen activator, urokinase (PLAU), budding uninhibited by benzimidazoles 3, HOX transcript antisense RNA, and euchromatic histone-lysine methyltransferase 2 (EHMT2). Using the risk score as an independent prognostic factor combined with clinicopathological features, the nomogram accurately predicted the overall survival (OS) of individual patients with ESCA. Gene ontology (GO) enrichment analysis indicated that the primary molecular roles included histone methyltransferase function, binding to C2H2 zinc finger domains, and histone-lysine N-methyltransferase activity. GSEA revealed that the high-risk cohort was connected to cytokine-cytokine receptor interaction, graft-versus-host disease, and hematopoietic cell lineage, whereas the low-risk cohort was related to arachidonic acid metabolism, drug metabolism via cytochrome P450 and fatty acid metabolism. Drug sensitivity tests showed that 16 drugs were positively correlated, and 3 drugs were negatively correlated with ARG characteristic scores. Our study developed 5 ARG signatures as biomarkers for patients with ESCA, providing an important reference for the individualized treatment of this disease.

An Antisense Long Non-Coding RNA, LncRsn, Is Involved in Sexual Reproduction and Full Virulence in Fusarium graminearum.

Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is a devastating crop disease that leads to significant declines in wheat yield and quality worldwide. Long non-coding RNAs (lncRNAs) are found to play significant functions in various biological processes, but their regulatory functions in the sexual reproduction and pathogenicity of F. graminearum have not been studied extensively. This study identified an antisense lncRNA, named lncRsn, located in the transcription initiation site region between the 5'-flanking gene FgSna and the 3'-flanking gene FgPta. A deletion mutant of lncRsn (ΔlncRsn) was constructed through homologous recombination. ΔlncRsn exhibited huge reductions in pathogen and sexual reproduction. Additionally, the deletion of lncRsn disrupted the biosynthesis of deoxynivalenol (DON) and impaired the formation of infection structures. RT-qPCR analysis reveals that lncRsn may negatively regulate the transcription of the target gene FgSna. This study found that lncRsn plays an important role in sexual and asexual reproduction, pathogenicity, virulence, osmotic stress, and cell wall integrity (CWI) in F. graminearum. Further characterization of pathogenesis-related genes and the reaction between lncRsn and protein-coding genes will aid in developing novel approaches for controlling F. graminearum diseases.

Molecular mechanism underlying the protective effects of ischemic preconditioning in total knee arthroplasty

ProposeTo investigate the molecular mechanisms underlying the protective effects of ischemic preconditioning (IPC) in patients undergoing total knee arthroplasty. MethodsGSE21164 was extracted from an online database, followed by an investigation of differentially expressed genes (DEGs) between IPC treatment samples at 2 time points (T0T and T1T). Function and pathway enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed to identify hub genes according to 5 different algorithms, followed by enrichment analysis. In addition, long noncoding RNAs (lncRNAs) were identified between the T0T and T1T samples. Furthermore, a competing endogenous RNA network was predicted based on the identified lncRNA-messenger RNA (mRNA), lncRNA-microRNA (miRNA), and mRNA-miRNA relationships revealed in this study. Finally, a drug-gene network was investigated. Statistical analyses were performed using GraphPad Prism 8.0. Differences between groups were determined using an unpaired t-test. p < 0.05 was considered significant. ResultsA total of 343 DEGs at T0 and 10 DEGs at T1 were identified and compared with their respective control groups, followed by 100 DEGs between T0T and T1T. Based on these 100 DEGs, protein-protein interaction network analysis revealed 9 hub genes, mainly with mitochondria-related functions and the carbon metabolism pathway. Six differentially expressed lncRNAs were investigated between T0T and T1T. A competing endogenous RNA network was constructed using 259 lncRNA–miRNA–mRNA interactions, including alpha-2-macroglobulin antisense RNA 1-miR-7161-5p-iron-sulfur cluster scaffold. Finally, 13 chemical drugs associated with the hub genes were explored. ConclusionIron-sulfur cluster scaffold may promote IPC-induced ischemic tolerance mediated by alpha-2-macroglobulin antisense RNA 1-miR-7161-5p axis. Moreover, IPC may induce a protective response after total knee arthroplasty via mitochondria-related functions and the carbon metabolism pathway, which should be further validated in the near future.

The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences. GMDS-AS1, an antisense RNA of GMDS, was discovered to have the potential to be an oncogene. We have acquired and analyzed relevant data to understand better how GMDS-AS1 and its lncRNA work physiologically and in tumorigenesis and progression. Additionally, we have looked into the possible effects of these molecules on cancer treatment approaches and patient outcomes. The physiological roles and putative processes of GMDS and lncRNA GMDS-AS1 throughout the development and progression of tumors have been assembled and examined. We also examined how these chemicals might affect patient prognosis and cancer therapy approaches. GMDS and GMDS-AS1 were determined to be research subjects by searching and gathering pertinent studies using the PubMed system. The analysis of these research articles demonstrated the close relationship between GMDS and GMDS-AS1 and tumorigenesis and the factors that influence them. GMDS plays a vital role in regulating fucosylation. The related antisense gene GMDS-AS1 affects the biological behaviors of cancer cells through multiple pathways, including the key processes of proliferation, migration, invasion, and apoptosis, providing potential biomarkers and therapeutic targets for cancer treatment and prognosis assessment.

The Pivotal Function of SLC16A1 and SLC16A1-AS1 in Cancer Progress: Molecular Pathogenesis and Prognosis.

More than 300 membranes make up the SLC family of transporters, utilizing an ion gradient or electrochemical potential difference to move their substrates across biological membranes. The SLC16 gene family contains fourteen members. Proton-linked transportation of monocarboxylates can be promoted by the transporters MCT1, which the SLC16A1 gene family encodes. Glycolysis is constitutively up-regulated in cancer cells, and the amount of lactate produced as a result is correlated with prognosis. Further speaking, SLC16A1 plays an essential role in controlling the growth and spread of tumors, according to mounting evidence. Additionally, LncRNAs are the collective term for all genes that produce RNA transcripts longer than 200 nucleotides but do not convert into proteins. It has steadily developed into a hub for research, offering an innovative approach to tumor study as technology related to molecular biology advances. The growing study has uncovered SLC16A1-AS1, an RNA that acts as an antisense to SLC16A1, which is erroneously expressed in various types of cancers. Therefore, we compiled the most recent information on the physiological functions and underlying processes of SLC16A1 and the LncRNA SLC16A1-AS1 during tumor development to explore their impact on cancer treatment and prognosis. We compiled the most recent information on the physiological functions and underlying processes of SLC16A1 and the LncRNA SLC16A1-AS1 during tumor development to explore their impact on cancer treatment and prognosis. Relevant studies were retrieved and collected through the PubMed system. After determining SLC16A1 and SLC16A1-AS1 as the research object, we found a close relationship between SLC16A1 and tumorigenesis as well as the influencing factors through the analysis of the research articles. SLC16A1 regulates lactate chemotaxis while uncovering SLC16A1- AS1 as an antisense RNA acting through multiple pathways; they affect the metabolism of tumor cells and have an impact on the prognosis of patients with various cancers.

LncRNA MACC1-AS1 facilitates the cell growth of small cell lung cancer by sequestering miR-579-3p and mediating NOTCH1-pathway.

As reported, long non-coding RNAs (lncRNAs) have been confirmed to be of great importance in regulating the progression of diseases, especially of cancers. LncRNA MACC1 antisense RNA 1 (MACC1-AS1) has been studied in some cancers, whereas its biological role and underlying mechanism is still unclear in small cell lung cancer (SCLC). In the current research, we found high level of MACC1-AS1 in SCLC cells. Subsequently, it was discovered that MACC1-AS1 knockdown considerably restrained the proliferative and migratory ability of SCLC cells by inducing the apoptosis. Importantly, the knockdown of MACC1-AS1 inhibited protein levels of genes of NOTCH pathway, and NOTCH pathway activator (Jagged1) countervailed the inhibition of MACC1-AS1 depletion on SCLC cell growth. Further, the deficiency of NOTCH1 hampered SCLC cell growth. More importantly, miR-579-3p was identified as a downstream gene of MACC1-AS1 and thereby targeted to NOTCH1. In addition, miR-579-3p repression recovered the suppressive role of MACC1-AS1 knockdown in NOTCH1 expression. Rescue assays indicated that repressed SCLC cell growth caused by MACC1-AS1 knockdown could be reserved by miR-579-3p repression or NOTCH1 overexpression. In brief, lncRNA MACC1-AS1 boosted SCLC cell growth via sequestering miR-579-3p and mediating NOTCH1-pathway.