LncRNA RP1-86C11.7 exacerbates the glioma progression and oncogenicity by hsa-miR-144-3p/TFRC signaling.
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ABSTRACT:
SUBMITTER: Ma Q
PROVIDER: S-EPMC8484814 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveColon cancer is a common malignant tumor of the gastrointestinal system, which is characterized by high morbidity and mortality. The purpose of this study was to analyze the expression and biological role of miR-181a-2-3p in colon cancer and to investigate the molecular mechanism of its regulatory effect on colon cancer through stimulator of interferon genes (STING).MethodsReal-time reverse transcription polymerase chain reaction (qRT-PCR) assay was used to detect the expression of miR-181a-2-3p in colon cancer cell lines and normal intestinal epithelial cells. After overexpression of miR-181a-2-3p in colon cancer cell lines SW480 and HT29, cells were examined by CCK8, Transwell, and flow cytometry assays for alterations in proliferation, migration, apoptosis, and cell cycle. Target genes of miR-181a-2-3p were predicted by bioinformatics and validated by dual luciferase assays. Rescue experiments were performed to explore the role of STING in the effect of miR-181a-2-3p. The effect of miR-181a-2-3p on colon cancer proliferation in vivo was validated by nude mouse tumorigenicity assay.ResultsmiR-181a-2-3p was lowly expressed in both colon cancer tissues and cell lines. Overexpression of miR-181a-2-3p led to reduced proliferation and migration, increased apoptosis, and altered cell cycle in colon cancer cell lines SW480 and HT29. STING was a target gene of miR-181a-2-3p. Increased STING expression partially counteracted the effect of overexpression of miR-181a-2-3p on colon cancer cell lines. miR-181a-2-3p also suppressed colon cancer proliferation in vivo.ConclusionmiR-181a-2-3p inhibits the proliferation and oncogenicity of colon cancer, and its molecular mechanism could be inhibited by STING.
| S-EPMC11346793 | biostudies-literature
Project description:Advanced age represents one of the major risk factors for Parkinson's Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson's Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson's Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson's Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson's Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson's Disease patients, and healthy siblings of Parkinson's Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson's Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson's Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson's Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson's Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson's Disease.
| S-EPMC8789812 | biostudies-literature
Project description:ObjectiveThis study explores LncRNA TM1-3P effects on the proliferation, apoptosis, and inflammatory response of fibroblasts in osteoarthritis (OA) and its underlying mechanism.MethodsBioinformatics was performed to analyze OA disease-related genes, miRNA profiles, and function. The targeted regulation of LncRNA TM1-3P and miR-144-3p, ONECUT2 and miR-144-3p were analyzed by dual luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP), and RNA pull down. Histopathological morphology of the knee joint was observed by hematoxylin-eosin (HE) and Annona Red O/Fast Green. The expressions of mRNAs and proteins were detected by RT-qPCR, Western blot, and immunohistochemistry. Unpaired T test was used between groups, and the one-way analysis of variance of repeated measurement data was applied for multi-group comparison, following Tukey's post-test.ResultsONECUT2 and Smurf2 genes were significantly elevated in the osteoarthritis group compared with the normal group (P < 0.001, P < 0.001). Expressions of ONECUT2 and LncRNA TM1-3P were increased, and expression of miR-144-3p was decreased in interleukin (IL)-1β-induced human fibroblast synovial cells (hFSCs) (mRNA: 1.06 ± 0.24 vs. 3.29 ± 0.73, proteins: 0.22 ± 0.03 vs. 0.46 ± 0.22, 1.23 ± 0.22 vs. 3.76 ± 0.73, 1.06 ± 0.25 vs. 0.37 ± 0.13, P < 0.01, P < 0.001, P < 0.01, P < 0.05). Overexpression of miR-144-3p down-regulated the ONECUT2 expression, reduced cell proliferation, promoted apoptosis in hFSCs induced by IL-1β (mRNA: 0.89 ± 0.14 vs. 0.15 ± 0.01, P < 0.05; proteins: 0.46 ± 0.01 vs. 0.23 ± 0.01, P < 0.001; CCK8: 1.88 ± 0.07 vs. 1.65 ± 0.07; P < 0.05; EDU: 55.82 ± 1.44 vs 40.57 ± 2.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.0001). Overexpression of LncRNA TM1-3P up-regulated the expression of ONECUT2, promoted cell proliferation, and inhibited apoptosis (mRNA: 0.9 ± 0.09 vs 1.94 ± 0.12, P < 0.05; proteins: 0.61 ± 0.05 vs 0.76 ± 0.03, P > 0.05; CCK8: 2.07 ± 0.05 vs 2.47 ± 0.06; P < 0.01; EDU: 52.67 ± 1.17 vs 60.06 ± 3.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.001), which were reversed by the overexpression of miR-144-3p treatment (mRNA: 1.82 ± 0.07 vs 0.31 ± 0.07, P < 0.0001; proteins: 0.74 ± 0.02 vs 0.35 ± 0.01, P < 0.01; CCK8: 2.41 ± 0.01 vs 1.67 ± 0.02; P < 0.0001; EDU: 66.85 ± 2.86 vs 44.68 ± 1.97, P < 0.0001; apoptosis: 7.19 ± 0.19 vs 13.36 ± 0.53, P < 0.0001). Silencing LncRNA TM1-3P attenuated the injury of knee joint tissue, down-regulated the expression of ONECUT2, Smurf2, IL-1β, IL-6, TNF-α, and improved the expression of Rap1 in rats (0.71 ± 0.04 vs 0.48 ± 0.02, 0.68 ± 0.06 vs 0.36 ± 0.02, 0.74 ± 0.03 vs 0.49 ± 0.04, 0.78 ± 0.01 vs 0.54 ± 0.03, 0.68 ± 0.02 vs 0.4 ± 0.04, 0.24 ± 0.01 vs 0.4 ± 0.03, P < 0.05, P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.05).ConclusionLncRNA TM1-3P improved inflammation and damage of knee joints in OA rats through miR-144-3p/ONECUT2 axis, providing a new theoretical basis for gene therapy of OA.
| S-EPMC9627084 | biostudies-literature
Project description:Glioma remains to be an aggressive type of cancer with poor prognosis irrespective of the type of standard treatment applied. Therefore, identification of accurate early diagnostic methods and therapeutic strategies for glioma is imperative for the treatment of this disease. The expression of a number of miRNAs in glioma have been reported to be associated with the regulation of tumorigenic progression, cancer cell proliferation, metastasis, invasion, angiogenesis and drug resistance. The aim of the present study was to assess the function of the microRNA (miR/miRNA)-144-3p/BCL6 axis in glioma. Reverse transcription-quantitative PCR was used to measure miR-144-3p and BCL6 expression. Western blotting was used for measuring BCL6 expression. Luciferase reporter assay was used to assess the association between miR-144-3p and BCL6 and a tumor xenograft model was established for assess tumor growth. The data demonstrated that miR-144-3p was decreased whereas BCL6 expression was increased in glioma tissues compared with those in healthy human brain tissues, where miR-144-3p suppressed BCL6 expression by targeting the 3'-UTR sequence of BCL6. miR-144-3p overexpression alleviated proliferation and invasion in U251 cells whereas transfection with the BCL6-overexpressing plasmid rescued the suppressive effects of miR-144-3p upregulation on the proliferation and invasion of U251 cells. In addition, miR-144-3p overexpression and BCL6 downregulation inhibited tumor progression in a mouse tumor xenograft model. The present findings suggest that miR-144-3p and BCL6 may serve to be indicator of proliferation and invasion for patients with glioma. Furthermore, BCL6 may serve an important role in the miR-144-3p-mediated regulation of proliferation and invasion of glioma cells, where the miR-144-3p/BCL6 axis can be used to target patients with glioma therapeutically.
| S-EPMC8393981 | biostudies-literature
Project description:This study aimed to screen miRNA biomarkers for melanoma progression. Raw melanoma data were downloaded from the Gene Expression Omnibus (GSE34460, GSE35579, GSE18509, and GSE24996) and the Cancer Genome Atlas (TCGA). Then, all differentially expressed miRNAs (DEmiRNAs) between benign vs. primary, metastatic vs. benign, and metastatic vs. primary groups were obtained in the GSE34460 and GSE35579 datasets, and the miRNAs related to disease progression were further screened. Then, the miRNA-gene network was constructed, followed by enrichment, survival, and cluster analyses. Differentially expressed genes (DEGs), tumor-infiltrating immune cells, and tumor mutation burden (TMB) between subtypes were analyzed. miRNAs were verified in the GSE18509 and GSE24996 datasets. A total of 132 and 209 DEmiRNAs were obtained in the GSE34460 and GSE35579 datasets, respectively, and 27 DEmiRNAs related to disease progression were screened. hsa-miR-106b-5p, hsa-miR-27b-3p, and hsa-miR-141-3p had a higher degree and were regulated by numerous genes in the miRNA-gene network. Moreover, four miRNAs were associated with prognosis: hsa-let-7c-5p, hsa-miR-130b-3p, hsa-miR-142-3p, and hsa-miR-509-3p. Furthermore, the bidirectional hierarchical clustering of 27 miRNAs was classified into three subtypes, and TMB and four types of immune cells, including activated dendritic cells, naïve CD4 T cells, M1 macrophages, and plasma cells, showed significant differences among the three subtypes. The expression levels of most miRNAs in the GSE18509 and GSE24996 datasets were consistent with those in the training dataset. These miRNAs, including hsa-let-7c-5p, hsa-miR-130b-3p, and hsa-miR-142-3p, and activated dendritic cells, naïve CD4 T cells, M1 macrophages, and plasma cells may play vital roles in the pathogenesis of melanoma.
| S-EPMC9282999 | biostudies-literature
Project description:The aim of the present study was to identify the differentially expressed microRNAs (DEMs) between Lynch syndrome (LS) and the normal colonic (N-C) control samples, predict the target genes (TGs) and analyze the potential functions of the DEMs and TGs. The miRNA expression dataset GSE30454, which included data of 13 LS and 20 N-C tissue samples, was downloaded from the Gene Expression Omnibus. The classical t-test in Linear Models for Microarray Data package was used for DEM identification. TG prediction was performed using 5 databases. The regulatory network of the DEMs and their TGs was constructed using Cytoscape. Functional and pathway enrichment analysis was performed. The transcription factors (TFs), tumor-associated genes (TAG) and tumor suppressor genes (TSGs) were then identified. Three key DEMs hsa-miR-137, hsa-miR-520e, and hsa-miR-590-3p were identified. Hsa-miR-520e and hsa-miR-137 had 4 common TGs, including SNF related kinase, metal-regulatory transcription factor 1 (MTF1), round spermatid basic protein 1 and YTH N6-methyladenosine RNA binding protein 3; hsa-miR-590-3p and hsa-miR-137 had 14 common TGs, including NCK adaptor protein 1 (NCK1), EPH receptor A7, and stress-associated endoplasmic reticulum protein 1; hsa-miR-590-3p and hsa-miR-520e had 12 common TGs, including Krüppel-like factor (KLF) 13, twinfilin actin binding protein 1, and nuclear factor I B. Through the functional and pathway enrichments analysis, MTF1 was involved in regulation of gene expression and metabolic processes, and sequence-specific DNA binding TF activity. KLF13 was involved in regulation of gene expression and regulation of cellular metabolic processes. NCK1 was enriched in the axon guidance pathway. In addition, the functional and pathway enrichment analysis showed certain TGs, such as hypoxia-inducible factor 1α, AKT serine/threonine kinase 2, and rapamycin-insensitive companion of mammalian target of rapamycin, participated in the mTOR signaling pathway. The 3 key DEMs hsa-miR-137, hsa-miR-520e, and hsa-miR-590-3p may have important roles in the process of LS.
| S-EPMC4998582 | biostudies-literature
Project description:Sepsis can cause sepsis-associated encephalopathy (SAE), but whether SAE was induced or exacerbated by ferroptosis remains unknown. In this study, the rat sepsis model was constructed using the cecal ligation and puncture method. The blood-brain barrier (BBB) permeability was measured by Evans blue dye (EBD) in vivo. The levels of ROS, Fe ion, MDA, GSH, and GPX4 were assessed by enzyme-linked immunosorbent assay (ELISA). The exosomes isolated from serum were cultured with bEnd.3 cells for the in vitro analysis. Moreover, bEnd.3 cells cultured with 100 μM FeCl3 (iron-rich) were to simulate ferroptosis stress. The cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. A dual-luciferase reporter gene assay was performed to confirm the relationship between miR-9-5p with NEAT1, TFRC, and GOT1. In vivo, it is found that BBB permeability was damaged in model rats. Level of ROS, Fe ion, and MDA was increased, and level of GSH and GPX4 was decreased, which means ferroptosis was induced by sepsis. Exosome-packaged NEAT1 in serum was significantly upregulated in model rats. In vitro, it is found that NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. Overexpression of NEAT1 enhanced ferroptosis stress in bEnd.3 cells. Increased miR-9-5p alleviated sepsis-induced ferroptosis by suppressing the expression of TFRC and GOT1 both in vivo and in vitro. In conclusion, these findings suggest that sepsis induced high expression of serous exosome-derived NEAT1, and it might exacerbate SAE by promoting ferroptosis through regulating miR-9-5p/TFRC and GOT1 axis.
| S-EPMC8882117 | biostudies-literature
Project description:Objective Non-small cell lung cancer (NSCLC) explains about 80 percent of whole lung cancers, and its 5-year survival rate is impoverished, as when people are first diagnosed, 68% of whom are identified at a dangerous stage. The molecular mechanisms of NSCLC are still being explored. Methods GSE18842 and GSE19804 were exerted to scan for diversely expressed genes (DEGs) in NSCLC, and then we used GEPIA for the validation of DEGs expression. The prognostic values were determined through Kaplan–Meier analysis. Three target prediction databases indicated potential microRNAs (miRNAs), while miRNet predicted hsa-miR-1-3p′s upstream long non-coding RNAs (lncRNAs) and pseudogenes. UALCAN was utilized to identify the co-expressed genes of PAICS, while enrichment analysis on them was managed with Enrichr. Results We initially found that the gene expression level of cyclin B1 (CCNB1), cyclin-dependent kinases1 (CDK1), and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) had a notable increase in NSCLC. We predicted 6, 10, and 7 microRNAs to target CCNB1, CDK1, and PAICS, respectively. Among miRNA-mRNA (microRNA-messenger RNA) pairs, we deduced that the hsa-miR-1-PAICS axis was the most potential one to inhibit the occurrence of NSCLC. We also noted that the hsa-miR-1-3p-PAICS axis participated in regulating the process of mitosis with mechanical functions. Moreover, we identified 5 pseudogenes and 33 long non-coding RNAs (lncRNAs) that might inhibit the hsa-miR-1-3p-PAICS axis in NSCLC. Conclusions The pseudogene/lncRNA-hsa-miR-1-3p-PAICS is very important in NSCLC on the basis of this study, thus providing us with effective treatments and promising biomarkers for the diagnosis of NSCLC.
| S-EPMC9448537 | biostudies-literature
Project description:OBJECTIVE:Ovarian cancer is one of the most common and lethal cancer types in women. The molecular mechanism of ovarian cancer progression is still unclear. RESULTS:Here, we first reported that expression levels of three genes, GJB2, S100A2 and SPOCK2, were significantly higher in advanced stage than that in early stage of ovarian cancer, and upregulation of them indicated poor prognosis of patients with ovarian cancer. Subsequently, 8, 6 and 20 miRNAs were predicted to target GJB2, S100A2 and SPOCK2, respectively. Among these miRNA-mRNA pairs, hsa-miR-363-3p-SPOCK2 axis was the most potential in suppressing progression of ovarian cancer. Mechanistically, we found that hsa-miR-363-3p-SPOCK2 axis was involved in regulation of actin cytoskeleton. Moreover, 6 pseudogenes and 8 lncRNAs were identified to potentially inhibit hsa-miR-363-3p-SPOCK2 axis in ovarian cancer. CONCLUSIONS:Collectively, we elucidate a regulatory role of pseudogene/lncRNA-hsa-miR-363-3p-SPOCK2 pathway in progression of ovarian cancer, which may provide effective therapeutic approaches and promising prognostic biomarkers for ovarian cancer. MATERIALS AND METHODS:Differentially expressed genes (DEGs) in ovarian cancer were first screened using GSE12470, after which DEGs expression were validated using GEPIA. Kaplan-Meier analysis was employed to assess the prognostic values. Potential miRNAs were predicted by seven target prediction databases, and upstream lncRNAs and pseudogenes of hsa-miR-363-3p were forecasted through miRNet or starBase. UALCAN and starBase were used to obtain the co-expressed genes of SPOCK. Enrichment analysis for these co-expressed genes was performed by Enrichr.
| S-EPMC6932902 | biostudies-literature
Project description:Accumulating evidences indicate that long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) promotes the progression of glioma. In this study, we postulated that NEAT1 may act as a miR-128-3p sponge. Relative levels of NEAT1 and miR-128-3p expression in human glioma samples and GBM cells were detected using quantitative real-time PCR. By means of CCK-8 assays, transwell assays, and flow cytometric analysis, the biological functions of miR-128-3p and NEAT1 were investigated in U87MG and U251MG human GBM cell lines with stable miR-128-3p and NEAT1 knockdown or overexpression. The luciferase reports, RNA pull-down assay, and RNA immunoprecipitation assay were conducted to determine the relevance of NEAT1 and miR-128-3p in glioma. As a result, high expression of NEAT1 and lack of miR-128-3p were observed in glioma specimens and cells. By binding to anti-oncogene miR-128-3p in the nucleus, NEAT1 enhanced tumorigenesis and glioma development. Further experiments suggested that ITGA5 expression was increased in glioma tissues and was found to be connected with miR-128-3p. Additionally, NEAT1 facilitated ITGA5 expression via competitively binding to miR-128-3p. For this reason, ITGA5 would not be decomposed by miR-128-3p and could activate FAK signaling pathway, thereby promoting cell growth. Collectively, these results indicated that the NEAT1/miR-128-3p/ITGA5 axis was involved in glioma initiation and progression, and might offer a potential novel strategy for treatment of glioma.
| S-EPMC8497354 | biostudies-literature