Triterpenes from Ganoderma lucidum inhibit hepatocellular carcinoma by regulating enhancer-associated lncRNA in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum) has been widely used as adjuvant of anti-tumor therapy for variety tumors. The bioactive ingredients of G. lucidum mainly include triterpenes, such as Ganoderic acid A, Ganoderic acid B, Ganoderenic acid A, Ganoderenic acid B, Ganoderenic acid D, and Ganoderic acid X. However, the effects and underlying mechanisms of G. lucidum are often challenging in hepatocellular carcinoma (HCC) treatment. AIM OF THE STUDY: To explore the potential role and mechanism of enhancer-associated lncRNAs (en-lncRNAs) in G. lucidum treated HCC through the in vivo and in vitro experiments. MATERIALS AND METHODS: Hepa1-6-bearing C57 BL/6 mice model were established to evaluate the therapeutic efficacy of G. lucidum treated HCC. Ki67 and TUNEL staining were used to detect the tumor cell proliferation and apoptosis in vivo. The Mouse lncRNA 4*180K array was implemented to identify the differentially expressed (DE) lncRNAs and mRNAs of G. lucidum treated tumor mice. The constructed lncRNA-mRNA co-expression network and bioinformatics analysis were used to selected core en-lncRNAs and its neighboring genes. The UPLC-MS method was used to identify the triterpenes of G. lucidum, and the in vitro experiments were used to verify which triterpene monomers regulated en-lncRNAs in tumor cells. Finally, a stable knockdown/overexpression cell lines were used to confirm the relationship between en-lncRNA and neighboring gene. RESULTS: Ki67 and TUNEL staining demonstrated G. lucidum significantly inhibited tumor growth, suppressed cell proliferation and induced apoptosis in vivo. Transcriptomic analysis revealed the existence of 126 DE lncRNAs high correlated with 454 co-expressed mRNAs in G. lucidum treated tumor mice. Based on lncRNA-mRNA network and qRT-PCR validation, 6 core lncRNAs were selected and considered high correlated with G. lucidum treatment. Bioinformatics analysis revealed FR036820 and FR121302 might act as enhancers, and qRT-PCR results suggested FR121302 might enhance Popdc2 mRNA level in HCC. Furthermore, 6 main triterpene monomers of G. lucidum were identified by UPLC-MS method, and in vitro experiments showed FR121302 and Popdc2 were significantly suppressed by Ganoderenic acid A and Ganoderenic acid B, respectively. The knock/overexpression results demonstrated that FR121302 activating and enhancing Popdc2 expression levels, and Ganoderenic acid A and Ganoderenic acid B dramatically suppressed FR121302 and decreased Popdc2 level in Hepa1-6 cells. CONCLUSIONS: Enhancer-associated lncRNA plays a crucial role as an enhancer during hepatocarcinogenesis, and triterpenes of G. lucidum significantly inhibited tumor cell proliferation and induced apoptosis by regulating en-lncRNAs. Our study demonstrated Ganoderenic acid A and Ganoderenic acid B suppressed en-lncRNA FR121302 may be one of the critical strategies of G. lucidum inhibit hepatocellular carcinoma growth.

The construction and experimental verification of a 6-LncRNA model based on Lactic acid metabolism in the tumor microenvironment of Wilms tumor.

BACKGROUND: Lactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. METHODS: Gene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. RESULTS: The immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor's development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. CONCLUSION: This study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.

lncRNA PVT1 silencing inhibits gastric cancer cells' progression via enhancing chemosensitivity to paclitaxel.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide because of its high morbidity and the absence of effective therapies. Even though paclitaxel is a powerful anticancer chemotherapy drug, recent studies have indicated its ineffectiveness against GC cells. Long non-coding RNA (lncRNA) PVT1 has a high expression in GC cells and increases the progression of tumors via inducing drug resistance. In the present study, the effects of the siRNA-mediated lncRNA PVT1 gene silencing along with paclitaxel treatment on the rate of apoptosis, growth, and migration of AGS GC cells were investigated. AGS cells were cultured and then transfected with siRNA PVT1 using electroporation. The MTT test was used to examine the effect of treatments on the viability of cultured cells. Furthermore, the flow cytometry method was used to evaluate the impact of treatments on the cell cycle process and apoptosis induction in GC cells. Finally, the mRNA expression of target genes was assessed using the qRT-PCR method. The results showed that lncRNA PVT1 gene suppression, along with paclitaxel treatment, reduces the viability of cancer cells and significantly increases the apoptosis rate of cancer cells and the number of cells arrested in the G2/M phase compared to the control group. Based on the results of qRT-PCR, combined treatment significantly decreased the expression of MMP3, MMP9, MDR1, MRP1, Bcl-2, k-Ras, and c-Myc genes and increased the expression of the Bax gene compared to the control group. The results of our study showed that lncRNA PVT1 gene targeting, together with paclitaxel treatment, induces apoptosis, inhibits growth, alleviates drug resistance, and reduces the migratory capability of GC cells. Therefore, there is a need for further investigations to evaluate the feasibility and effectiveness of this approach in vivo in animal models.

Identification of telomere-related lncRNAs and immunological analysis in ovarian cancer.

Background: Ovarian cancer (OC) is a global malignancy characterized by metastatic invasiveness and recurrence. Long non-coding RNAs (lncRNAs) and Telomeres are closely connected with several cancers, but their potential as practical prognostic markers in OC is less well-defined. Methods: Relevant mRNA and clinical data for OC were sourced from The Cancer Genome Atlas (TCGA) database. The telomere-related lncRNAs (TRLs) prognostic model was established by univariate/LASSO/multivariate regression analyses. The effectiveness of the TRLs model was evaluated and measured via the nomogram. Additionally, immune infiltration, tumor mutational load (TMB), and drug sensitivity were evaluated. We validated the expression levels of prognostic genes. Subsequently, PTPRD-AS1 knockdown was utilized to perform the CCK8 assay, colony formation assay, transwell assay, and wound healing assay of CAOV3 cells. Results: A six-TRLs prognostic model (PTPRD-AS1, SPAG5-AS1, CHRM3-AS2, AC074286.1, FAM27E3, and AC018647.3) was established, which can effectively predict patient survival rates and was successfully validated using external datasets. According to the nomogram, the model could effectively predict prognosis. Furthermore, we detected the levels of regulatory T cells and M2 macrophages were comparatively higher in the high-risk TRLs group, but the levels of activated CD8 T cells and monocytes were the opposite. Finally, the low-risk group was more sensitive to anti-cancer drugs. The mRNA levels of PTPRD-AS1, SPAG5-AS1, FAM27E3, and AC018647.3 were significantly over-expressed in OC cell lines (SKOV3, A2780, CAOV3) in comparison to normal IOSE-80 cells. AC074286.1 were over-expressed in A2780 and CAOV3 cells and CHRM3-AS2 only in A2780 cells. PTPRD-AS1 knockdown decreased the proliferation, cloning, and migration of CAOV3 cells. Conclusion: Our study identified potential biomarkers for the six-TRLs model related to the prognosis of OC.

LncRNA LINC01664 promotes cancer resistance through facilitating homologous recombination-mediated DNA repair.

The intracellular responses to DNA double-strand breaks (DSB) repair are crucial for genomic stability and play an essential role in cancer resistance. In addition to canonical DSB repair proteins, long non-coding RNAs (lncRNAs) have been found to be involved in this sophisticated network. In the present study, we performed a loss-of-function screen for a customized siRNA Premix Library to identify lncRNAs that participate in homologous recombination (HR) process. Among the candidates, we identified LINC01664 as a novel lncRNA required for HR repair. Furthermore, LINC01664 knockdown significantly increased the sensitivity of cancer cells to DNA damage agents such as ionizing radiation and genotoxic drugs. Mechanistically, LINC01664 interacted with Sirt1 promoter and then activated Sirt1 transcription, which contributed to HR-mediated DNA damage repair. In summary, our findings revealed a new mechanism of LINC01664 in DNA damage repair, providing evidence for a potential therapeutic strategy for eliminating the treatment bottlenecks caused by cancer resistance to chemotherapy and radiotherapy.

LncRNA TUG1 regulates miR-34a-5p / SIRT6 to participate in benzene-induced hematotoxicity through PI3K / AKT /mTOR signaling pathway.

LncRNA TUG1 plays pivotal roles in various diseases. However, its exact roles in benzene - induced hematotoxicity remain unclear. Herein, we aimed to investigate the role and mechanism of TUG1 in hematoxic injuries caused by benzene. In the current study, TUG1 was found dramatically decreased in WBCs of benzene exposure workers and negatively correlated with benzene exposure duration and urine SPMA. In vitro assays demonstrated that TUG1 overexpression attenuated 1,4-BQ-caused suppression of cell viability and proliferation, and promotion of ROS generation and apoptosis via PI3K /AKT /mTOR pathway. Bioinformatic prediction and molecular assay validated miR-34a-5p was negatively regulated by TUG1. The miR-34a-5p was upregulated in 1,4-BQ treated cells and downregulated in TUG1 overexpression cells. Moreover, miR-34a-5p upregulation partially reversed the protective effects of TUG1 overexpression on 1,4-BQ - caused cytotoxicity. Furthermore, SIRT6 was a downstream target gene of miR-34a-5p, whose expression was reduced in miR-34a-5p upregulation cells and elevated in TUG1 overexpression cells. Upregulated SIRT6 could counteract accelerated cytotoxicity mediated by miR-34a-5p upregulation after 1,4-BQ treatment. Taken together, our study revealed that the critical role of the TUG1 / miR-34a-5p / SIRT6 axis in benzene-caused hematotoxicity, and provided scientific basis for further understanding the epigenetic regulatory mechanisms underlying benzene hematotoxicity.

Targeting Long Non-Coding RNA H19 as a Therapeutic Strategy for Liver Disease.

The liver has the function of regulating metabolic equilibrium in the human body, and the majority of liver disorders are chronic conditions that can significantly impair health. Recent research has highlighted the critical role of long noncoding RNAs (lncRNAs) in liver disease pathogenesis. LncRNA H19, an endogenous noncoding single-stranded RNA, exerts its influence through epigenetic modifications and affects various biological processes. This review focuses on elucidating the key molecular mechanisms underlying the regulation of H19 during the progression and advancement of liver diseases, aiming to highlight H19 as a potential therapeutic target and provide profound insights into the molecular underpinnings of liver pathologies.

RNA in axons, dendrites, synapses and beyond.

In neurons, a diverse range of coding and non-coding RNAs localize to axons, dendrites, and synapses, where they facilitate rapid responses to local needs, such as axon and dendrite extension and branching, synapse formation, and synaptic plasticity. Here, we review the extent of our current understanding of RNA subclass diversity in these functionally demanding subcellular compartments. We discuss the similarities and differences identified between axonal, dendritic and synaptic local transcriptomes, and discuss the reported and hypothesized fates and functions of localized RNAs. Furthermore, we outline the RNA composition of exosomes that bud off from neurites, and their implications for the biology of neighboring cells. Finally, we highlight recent advances in third-generation sequencing technologies that will likely provide transformative insights into splice isoform and RNA modification diversity in local transcriptomes.

An overview of lncRNA NEAT1 contribution in the pathogenesis of female cancers; from diagnosis to therapy resistance.

Despite the ongoing progress in detecting and treating cancer, there is still a need for extensive research into the molecular mechanisms involved in the emergence, progression, and resistance to recurrence of female reproductive tissue-specific cancers such as ovarian, breast, cervical, and endometrial cancers. The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) that exhibits increased expression in female tumors. Moreover, elevated levels of NEAT1 have been associated with poorer survival outcomes in cancer patients. NEAT1 plays a pivotal role in driving tumor initiation through modulating the expression of genes involved in various aspects of tumor cell proliferation, epithelial-to-mesenchymal transition (EMT), metastasis, chemoresistance, and radio-resistance. Mechanistically, NEAT1 acts as a scaffold RNA molecule via interacting with EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit), thereby influencing the expression of downstream effectors of EZH2. Additionally, NEAT1 functions as a competing endogenous RNA (ceRNA) by microRNAs (miRNAs) sponging, consequently altering the expression levels of their target genes during the development of female cancers. This comprehensive review aims to shed light on the latest insights regarding the expression pattern, biological functions, and underlying mechanisms governing the function and regulation of NEAT1 in tumors. Furthermore, particular emphasis is placed on its clinical significance as a novel diagnostic biomarker and a promising therapeutic target for female cancers.

[The Expression of TP53TG1, LINC00342, MALAT1, H19, and MEG3 Long Noncoding RNAs in Type 2 diabetes mellitus].

Type 2 diabetes is a complex and multifactorial metabolic disorder. The frequency of type 2 diabetes has dramatically increased worldwide. Long noncoding RNAs play a regulatory role in pathological processes of type 2 diabetes. The aim of the study was to analyze TP53TG1, LINC00342, MALAT1, H19, and MEG3 lncRNAs in patients with type 2 diabetes and metabolic parameters, as well as the risk of diabetic retinopathy. Participants included 51 patients with diabetes and 70 healthy individuals. The expression of the TP53TG1 and LINC00342 genes was significantly decreased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was higher in diabetes patients. H19 gene expression was increased in the patients with diabetic retinopathy compared patients without retinopathy. TP53TG1, LINC00342, and MEG3 expression was decreased in patients with diabetic retinopathy and MALAT1 expression was increased. H19 is positively correlated with triglyceride levels; TP53TG1 and LINC00342 are positively correlated with HbA1c levels and fasting glucose levels. MALAT1 is negatively correlated with HDL levels and positively correlated with LDL levels. A decrease in the expression level of TP53TG1 and LINC00342 and an increase in the level of MALAT1 in diabetes, as well as an association with glycemic control, indicate the role of the studied noncoding RNAs in the development of type 2 diabetes mellitus and retinopathy and can be considered as candidates for early diagnosis of type 2 diabetes.

LncRNA-SNHG16 Protects Against Oxidative Stress-Induced Vascular Endothelial Cell Injury in Cardiovascular Diseases by Regulating the miR-23a-3p-GLS-Glutamine Metabolism Axis.

Cardiovascular diseases are disorders of the heart and vascular system that cause high mortality rates worldwide. Vascular endothelial cell (VEC) injury caused by oxidative stress (OS) is an important event in the development of various cardiovascular diseases, including ischemic heart disease. This study aimed to investigate the critical roles and molecular mechanisms of long non-coding RNA (lncRNA) SNHG16 in regulating vascular endothelial cell injury under oxidative stress. We demonstrated that SNHG16 was significantly downregulated and miRNA-23a-3p was notably induced in human vascular endothelial cells under OS. Overexpressing SNHG16 or silencing miR-23a-3p effectively mitigated the OS-induced VEC injury. Additionally, glutamine metabolism of VECs was suppressed under OS. SNHG16 protected the OS-suppressed glutamine metabolism, while miR-23a-3p functioned oppositely in VECs. Furthermore, SNHG16 downregulated miR-23a-3p by sponging miR-23a-3p, which direct targeted the glutamine metabolism enzyme, GLS. Finally, restoring miR-23a-3p in SNHG16-overexpressing VECs successfully reversed the protective effect of SNHG16 on vascular endothelial cell injury under OS. In summary, our results revealed the roles and molecular mechanisms of the SNHG16-mediated protection against VEC injury under OS by modulating the miR-23a-3p-GLS pathway.

SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function.

In this study, we characterize a novel lncRNA-producing gene locus that we name Syntenic Cardiovascular Conserved Region-Associated lncRNA-6 (scar-6) and functionally validate its role in coagulation and cardiovascular function. A 12-bp deletion of the scar-6 locus in zebrafish (scar-6gib007Δ12/Δ12) results in cranial hemorrhage and vascular permeability. Overexpression, knockdown and rescue with the scar-6 lncRNA modulates hemostasis in zebrafish. Molecular investigation reveals that the scar-6 lncRNA acts as an enhancer lncRNA (elncRNA), and controls the expression of prozb, an inhibitor of factor Xa, through an enhancer element in the scar-6 locus. The scar-6 locus suppresses loop formation between prozb and scar-6 sequences, which might be facilitated by the methylation of CpG islands via the prdm14-PRC2 complex whose binding to the locus might be stabilized by the scar-6 elncRNA transcript. Binding of prdm14 to the scar-6 locus is impaired in scar-6gib007Δ12/Δ12 zebrafish. Finally, activation of the PAR2 receptor in scar-6gib007Δ12/Δ12 zebrafish triggers NF-κB-mediated endothelial cell activation, leading to vascular dysfunction and hemorrhage. We present evidence that the scar-6 locus plays a role in regulating the expression of the coagulation cascade gene prozb and maintains vascular homeostasis.

Current knowledge of antisense long non-coding RNA in the occurrence and prognosis of skull base tumors.

Antisense long non-coding RNA (AS-lncRNA) represents a novel class of RNA molecules. In recent years, it has been discovered that AS-lncRNAs play crucial roles in various biological processes, particularly in the onset and progression of tumors. Skull base tumors, originating from the base of the brain, exhibit specific expression patterns of AS-lncRNA which correlate significantly with clinical characteristics. This makes AS-lncRNA a promising candidate as a tumor marker. Functional studies have revealed that AS-lncRNAs can regulate gene expression by acting as miRNA sponges and interacting with RBPs. Consequently, they play pivotal roles in tumor cell cycle, apoptosis, angiogenesis, invasion, and metastasis processes. Further exploration into the mechanisms of AS-lncRNA in tumors holds substantial theoretical significance for deeper insights into the etiology, pathogenesis, and RNA dynamics of skull base tumors. Moreover, AS-lncRNA could serve as molecular markers or potential targets for early diagnosis. Their potential extends to efficacy assessment, prognosis prediction, and gene therapy, suggesting broad clinical applications. In summary, AS-lncRNA emerges as a promising molecular marker implicated in the onset and progression of skull base tumors.

The prognostic significance of lncRNA FGD5-AS1 in various malignancies: a meta-analysis.

Background: Cancer is widely recognized as a prominent contributor to global mortality due to factors such as delayed diagnosis, unfavorable prognosis, and high likelihood of recurrence. FGD5 transcription factor G antisense RNA 1(FGD5-AS1), a newly identified long non-coding RNA, has emerged as a promising prognostic biomarker, for malignancy prognosis. This meta-analysis aimed to assess the prognostic significance of FGD5-AS1 in various carcinomas. Methods: A systematic search was performed through five electronic databases to identify studies that investigating the role of FGD5-AS1 expression as a prognostic factor in carcinomas. The value of FGD5-AS1 in malignancies was estimated by odds ratios (ORs) and hazard ratios (HRs) with a corresponding 95% confidence intervals (CIs). Furthermore, the GEPIA database was used to further supplement our results. Results: This analysis included 12 studies with 642 cases covering eight cancer types. High FGD5-AS1 expression exhibited a significant correlation with poor overall survival(OS) (HR = 2.04, 95%CI [1.72, 2.42], P < 0.00001), advanced tumor stage (OR = 3.47, 95%CI [2.34, 5.14], P < 0.00001), lymph node metastasis(LNM) (OR = 1.79, 95% CI [1.20,2.67], P = 0.004), and larger tumor size (OR= 5.25, 95%CI [2.68, 10.30], P < 0.00001). Furthermore, the FGD5-AS1 expression was notably upregulated in six types of malignancies as verified using the GEPIA online gene analysis tool. Conclusions: The findings of this meta-analysis indicated that high FGD5-AS1 expression was significantly associated with poor prognosis in diverse cancer types, suggesting that FGD5-AS1 may be a promising biomarker for predicting cancer prognosis. Systematic review registration: https://www.york.ac.uk/inst/crd, identifier CRD42024552582.

Silencing the long noncoding RNA MALAT1 inhibits vitreous-induced epithelial-mesenchymal transition in RPE cells by regulating the PDGFRs/AKT axis.

PURPOSE: Epithelial-mesenchymal transition (EMT) is a crucial pathological process that contributes to proliferative vitreoretinopathy (PVR), and research indicates that factors present in the vitreous that target cells play pivotal roles in regulating EMT. Experimental studies have confirmed that rabbit vitreous (RV) promotes EMT in human retinal pigment epithelial (RPE) cells. The long noncoding RNA (lncRNA) MALAT1 has been implicated in EMT in various diseases. Thus, this study aimed to investigate the involvement of lncRNA MALAT1 in vitreous-induced EMT in RPE cells. METHODS: MALAT1 was knocked down in ARPE-19 cells by short hairpin RNA (shRNA) transfection. Reverse transcription PCR (RT‒PCR) was used to evaluate MALAT1 expression, and Western blotting analysis was used to measure the expression of EMT-related proteins. Wound-healing, Transwell, and cell contraction assays were conducted to assess cell migration, invasion, and contraction, respectively. Additionally, cell proliferation was assessed using the CCK-8 assay, and cytoskeletal changes were examined by immunofluorescence. RESULTS: MALAT1 expression was significantly increased in ARPE-19 cells cultured with RV. Silencing MALAT1 effectively suppressed EMT and downregulated the associated factors snail1 and E-cadherin. Furthermore, silencing MALAT1 inhibited the RV-induced migration, invasion, proliferation, and contraction of ARPE-19 cells. Silencing MALAT1 also decreased RV-induced AKT and P53 phosphorylation. CONCLUSIONS: In conclusion, lncRNA MALAT1 participates in regulating vitreous-induced EMT in human RPE cells; these results provide new insight into the pathogenesis of PVR and offer a potential direction for the development of antiproliferative drugs.

LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/ß-catenin signaling pathway.

OBJECTIVE: This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms. METHODS: RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent in situ hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/ß-catenin signaling pathway. RESULTS: Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (p < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (p < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of ß-catenin (p < 0.05), p-GSK-3ß (p < 0.05), Cyclin D1 (p < 0.05), PCNA (p < 0.05), and thus reduced the cell proliferation. CONCLUSION: NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/ß-catenin signaling.

Exosome-mediated transfer of lncRNA RP3-340B19.3 promotes the progression of breast cancer by sponging miR-4510/MORC4 axis.

BACKGROUND: This study aims to explore the molecular mechanism of lncRNA RP3-340B19.3 on breast cancer cell proliferation and metastasis and clinical significance of lncRNA RP3-340B19.3 for breast cancer. METHODS: The subcellular localization of lncRNA RP3-340B19.3 was identified using RNA fluorescence in situ hybridization (FISH). The expression of lncRNA RP3-340B19.3 in breast cancer cells, breast cancer tissues, as well as the serum and serum exosomes of breast cancer patients, was measured through quantitative RT-PCR. In the in vitro setting, we conducted experiments to observe the effects of RP3-340B19.3 on both cell migration and proliferation. This was achieved through the utilization of transwell migration assays as well as clone formation assays. Meanwhile, transwell migration assays and clone formation assays were used to observe the effects of MDA-MB-231-exosomes enriched in RP3-340B19.3 on breast cancer microenvironment cells MCF7 and BMMSCs. Additionally, western blotting techniques were used to assess the expression levels of proteins associated with essential cellular processes such as proliferation, apoptosis, and metastasis. In vivo, the impact of RP3-340B19.3 knockdown on tumour weight and volume was observed within a nude mice model. We aimed to delve into the intricate molecular mechanisms involving RP3-340B19.3 by using bioinformatics analysis, dual luciferase reporter gene experiments and western blotting. Moreover, the potential correlations between RP3-340B19.3 expression and various clinical pathological characteristics were analyzed. RESULTS: Our investigation revealed that RP3-340B19.3 was expressed in both the cytoplasm and nucleus, with a noteworthy increase in breast cancer cells. Notably, we found that RP3-340B19.3 exerted a promoting influence on the proliferation and migration of breast cancer cells, both in vitro and in vivo. MDA-MB-231-exosomes enriched in RP3-340B19.3 promoted the proliferation and migration of MCF7 and BMMSCs in vitro. Mechanistically, RP3-340B19.3 demonstrated the capability to modulate the expression of MORC4 by forming a complex with miR-4510. This interaction subsequently triggered the activation of the NF-κB and Wnt-ß-catenin signaling pathways. Furthermore, our study highlighted the potential diagnostic utility of RP3-340B19.3. We discovered its presence in the serum and exosomes of breast cancer patients, showing promising efficacy as a diagnostic marker. Notably, the diagnostic potential of RP3-340B19.3 was particularly significant in relation to distinguishing between different pathological types of breast cancer and correlating with tumour diameter. CONCLUSION: Our findings establish that RP3-340B19.3 plays a pivotal role in driving the proliferation and metastasis of breast cancer. Additionally, exosomes enriched in RP3-340B19.3 could influence MCF7 and BMMSCs in tumour microenvironment, promoting the progression of breast cancer. This discovery positions RP3-340B19.3 as a prospective novel candidate for a tumour marker, offering substantial potential in the realms of breast cancer diagnosis and treatment strategies.

Exploring potential roles of long non-coding RNAs in cancer immunotherapy: a comprehensive review.

Cancer treatment has long been fraught with challenges, including drug resistance, metastasis, and recurrence, making it one of the most difficult diseases to treat effectively. Traditional therapeutic approaches often fall short due to their inability to target cancer stem cells and the complex genetic and epigenetic landscape of tumors. In recent years, cancer immunotherapy has revolutionized the field, offering new hope and viable alternatives to conventional treatments. A particularly promising area of research focuses on non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), and their role in cancer resistance and the modulation of signaling pathways. To address these challenges, we performed a comprehensive review of recent studies on lncRNAs and their impact on cancer immunotherapy. Our review highlights the crucial roles that lncRNAs play in affecting both innate and adaptive immunity, thereby influencing the outcomes of cancer treatments. Key observations from our review indicate that lncRNAs can modify the tumor immune microenvironment, enhance immune cell infiltration, and regulate cytokine production, all of which contribute to tumor growth and resistance to therapies. These insights suggest that lncRNAs could serve as potential targets for precision medicine, opening up new avenues for developing more effective cancer immunotherapies. By compiling recent research on lncRNAs across various cancers, this review aims to shed light on their mechanisms within the tumor immune microenvironment.

As a novel prognostic model for breast cancer, the identification and validation of telomere-related long noncoding RNA signatures.

BACKGROUND: Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs. METHODS: We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model's prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR. RESULTS: We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we've discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment. CONCLUSION: As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.

Development of an immunogenic cell death-related lncRNAs signature for prognostic risk assessment in gastric cancer.

Background: Immunogenic cell death (ICD) is a functionally specialized form of apoptosis induced by endoplasmic reticulum (ER) stress and is associated with a variety of cancers, including gastric cancer (GC). In recent years, long non-coding RNAs (lncRNAs) have been shown to be important mediators in the regulation of ICD. However, the specific role and prognostic value of ICD-related lncRNAs in GC remain unclear. This study aims to develop an ICD-related lncRNAs signature for prognostic risk assessment in GC. Methods: The ICD-related lncRNAs signature (ICDlncSig) of GC was constructed by univariate Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) regression model and multivariate Cox regression analysis, and the signature was correlated with immune infiltration. The potential response of GC patients to immunotherapy was predicted by the tumor immune dysfunction and rejection (TIDE) algorithm. In vitro functional experiments were conducted to assess the impact of lncRNAs on the proliferation, migration, and invasion capabilities of GC cells. Results: We constructed a novel ICDlncSig and found that this signature could be used as a prognostic risk model to predict survival of GC patients by validating it in the training cohort, testing cohort and entire cohort. The robust predictive power of the signature was demonstrated by building a Nomogram based on ICDlncSig scores and clinical characteristics. Furthermore, immune cell subpopulations, expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. The in vitro functional experiments revealed that AP002954.1 and AP000695.1 can promote the proliferation, migration, and invasion of GC cells. Conclusions: In conclusion, our ICDlncSig model has significant predictive value for the prognosis of GC patients and may provide clinical guidance for individualized immunotherapy.