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1.
Journal of Zhejiang University. Science. B ; (12): 1106-1122, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1010586

RESUMO

With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.


Assuntos
Humanos , Fases de Leitura Aberta , Peptídeos , Glucose , Genoma , Doenças Metabólicas
2.
Biomedical and Environmental Sciences ; (12): 1136-1151, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1007893

RESUMO

OBJECTIVE@#Exosomal long noncoding RNAs (lncRNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lncRNAs in white matter hyperintensities (WMH).@*METHODS@#We used high-throughput sequencing to determine the differential expression (DE) profiles of lncRNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using qRT-PCR. The diagnostic potential of candidate exosomal lncRNAs was proven by binary logistic analysis and receiver operating characteristic (ROC) curves. The diagnostic value of DE exo-lncRNAs was determined by the area under the curve (AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lncRNAs in the subgroup was evaluated.@*RESULTS@#In our results, four DE exo-lncRNAs were identified, and ROC curve analysis revealed that exo-lnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities.@*CONCLUSION@#Plasma exosomal lncRNAs have potential diagnostic value in WMH. Moreover, exo-lnc_011797 is considered to be a predictor of the severity and location of WMH.


Assuntos
Humanos , RNA Longo não Codificante/genética , Substância Branca , Área Sob a Curva , Exossomos/genética , Sequenciamento de Nucleotídeos em Larga Escala
3.
Journal of Zhejiang University. Medical sciences ; (6): 139-147, 2023.
Artigo em Inglês | WPRIM | ID: wpr-982028

RESUMO

OBJECTIVES@#To construct a prognosis risk model based on long noncoding RNAs (lncRNAs) related to cuproptosis and to evaluate its application in assessing prognosis risk of bladder cancer patients.@*METHODS@#RNA sequence data and clinical data of bladder cancer patients were downloaded from the Cancer Genome Atlas database. The correlation between lncRNAs related to cuproptosis and bladder cancer prognosis was analyzed with Pearson correlation analysis, univariate Cox regression, Lasso regression, and multivariate Cox regression. Then a cuproptosis-related lncRNA prognostic risk scoring equation was constructed. Patients were divided into high-risk and low-risk groups based on the median risk score, and the immune cell abundance between the two groups were compared. The accuracy of the risk scoring equation was evaluated using Kaplan-Meier survival curves, and the application of the risk scoring equation in predicting 1, 3 and 5-year survival rates was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate Cox regression were used to screen for prognostic factors related to bladder cancer patients, and a prognostic risk assessment nomogram was constructed, the accuracy of which was evaluated with calibration curves.@*RESULTS@#A prognostic risk scoring equation for bladder cancer patients was constructed based on nine cuproptosis-related lncRNAs. Immune infiltration analysis showed that the abundances of M0 macrophages, M1 macrophages, M2 macrophages, resting mast cells and neutrophils in the high-risk group were significantly higher than those in the low-risk group, while the abundances of CD8+ T cells, helper T cells, regulatory T cells and plasma cells in the low-risk group were significantly higher than those in the high-risk group (all P<0.05). Kaplan-Meier survival curve analysis showed that the total survival and progression-free survival of the low-risk group were longer than those of the high-risk group (both P<0.01). Univariate and multivariate Cox analysis showed that the risk score, age and tumor stage were independent factors for patient prognosis. The ROC curve analysis showed that the area under the curve (AUC) of the risk score in predicting 1, 3 and 5-year survival was 0.716, 0.697 and 0.717, respectively. When combined with age and tumor stage, the AUC for predicting 1-year prognosis increased to 0.725. The prognostic risk assessment nomogram for bladder cancer patients constructed based on patient age, tumor stage, and risk score had a prediction value that was consistent with the actual value.@*CONCLUSIONS@#A bladder cancer patient prognosis risk assessment model based on cuproptosis-related lncRNA has been successfully constructed in this study. The model can predict the prognosis of bladder cancer patients and their immune infiltration status, which may also provide a reference for tumor immunotherapy.


Assuntos
Humanos , Linfócitos T CD8-Positivos , Prognóstico , RNA Longo não Codificante/genética , Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Cobre , Apoptose
4.
Journal of Integrative Medicine ; (12): 47-61, 2023.
Artigo em Inglês | WPRIM | ID: wpr-971646

RESUMO

OBJECTIVE@#Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.@*METHODS@#The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.@*RESULTS@#Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment.@*CONCLUSION@#Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.


Assuntos
Humanos , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , RNA Longo não Codificante/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , MicroRNAs/genética , Células Estreladas do Fígado/patologia , Cirrose Hepática/metabolismo , Proliferação de Células , Fatores de Crescimento Transformadores/farmacologia
5.
Neuroscience Bulletin ; (6): 440-452, 2023.
Artigo em Inglês | WPRIM | ID: wpr-971564

RESUMO

Non-coding RNAs (ncRNAs) are a class of functional RNAs that play critical roles in different diseases. NcRNAs include microRNAs, long ncRNAs, and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system (CNS) diseases. Mounting evidence indicates that ncRNAs play key roles in CNS diseases. Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.


Assuntos
Humanos , RNA não Traduzido/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Circular , Doenças do Sistema Nervoso Central/genética
6.
Indian J Pathol Microbiol ; 2022 Jun; 65(2): 288-295
Artigo | IMSEAR | ID: sea-223220

RESUMO

Background: Deregulation of long noncoding RNAs (lncRNAs) was considered one of the main characteristics of several human cancers. However, detailed genome-wide expression and functional significance studies of lnc RNAs in lung adenocarcinoma are still limited. This study aims to discover a new lncRNA that may play an important role in regulating the pathogenesis of lung adenocarcinoma (ADC). Methods: We conducted a comprehensive analysis of three Gene Expression Omnibus (GEO) microarray datasets and TCGA datasets. Differentially expressed lncRNAs between ADC and normal tissues were screened and verified using Gene Expression Profiling Interactive Analysis (GEPIA). Moreover, Kaplan-Meier plotter was used to construct the gene prognosis profile. The downstream targets of miRNA and related functional pathways were predicted and validated. Results: With microarray gene expression analysis, we found that only lncRNAs-PCAT6 was commonly upregulated among four datasets, and four lncRNAs (LINC00968, PGM5-AS1, LHFPL3-AS2 and SFTA1P) were significantly downregulated in the ADC samples as compared to the normal tissues. Meanwhile, for LHFPL3-AS2, high-risk patients showed better overall survival (HR=0.6 or 0.62; P < .0001 or P = 0.0014), overall survival from TCGA datasets (HR=0.72; P = 0.015) and recurrence-free survival (HR=0.72; P = 0.015). Then, LHFPL3-AS2 was predicted to bind to two miRNAs, miR-127-5p and miR-424-5p. Finally, validation and functional enrichment analysis of the downstream key mRNAs showed significant enrichment in some cancer-related pathways, such as cell adhesion in cancer and small cell lung cancer. Conclusions: Taken together, our study indicated that LHFPL3-AS2 was associated with tumorigenesis, and it could be used as a useful biomarker in the diagnosis, prognosis and treatment of ADC.

7.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 68(2): 170-175, Feb. 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1365349

RESUMO

SUMMARY OBJECTIVE: A growing volume of literature has suggested long noncoding RNAs (lncRNAs) as important players in tumor progression. In this study, we aimed to investigate the expression and prognostic value of lncRNA LINC00173 (LINC00173) in melanoma. METHODS: LINC00173 expression was measured in 163 paired cancerous and noncancerous specimen samples by real-time polymerase chain reaction. The correlations between LINC00173 expression with clinicopathological characteristics and prognosis were analyzed by chi-square test, log-rank test, and multivariate survival analysis. Receiver-operating characteristic curves were used for the assessment of the diagnostic value of LINC00173 for melanoma patients. RESULTS: The expression level of LINC00173 in melanoma specimens was distinctly higher than that in adjacent non-neoplasm specimens (p<0.01). Besides, LINC00173 was expressed more frequently in patients with advanced melanoma than in patients with early melanoma. Multivariate assays confirmed that LINC00173 expression level was an independent prognostic predictor of melanoma patients (p<0.05). CONCLUSION: Our data indicated that LINC00173 expression could serve as an unfavorable prognostic biomarker for melanoma patients.


Assuntos
Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Melanoma/diagnóstico , Melanoma/genética , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Estimativa de Kaplan-Meier
8.
Chinese Journal of Postgraduates of Medicine ; (36): 992-997, 2022.
Artigo em Chinês | WPRIM | ID: wpr-955438

RESUMO

Objective:To investigate the mechanism of long noncoding RNA (lncRNA) LBX2-AS1 regulating glioma cell proliferation, migration and apoptosis through epidermal growth factor receptor (EGFR) signaling pathway.Methods:From April 2018 to August 2021, glioma U251 cells (U251 cells for short) were divided into control group and observation group, with 4 strains in each group. The control group was routinely cultured, and the observation group was transfected with specific small interfering RNA (siRNA) targeting LBX2-AS1. The proliferation ability of U251 cells was detected by methyl thiazol tetrazolium method, the metastasis rate of U251 cells was detected by scratch test, the apoptosis rate of U251 cells was detected by flow cytometry, and the expression of total protein and vascular endothelial growth factor (VEGF), phosphorylated inositol 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), phosphorylated Ras (p-Ras) and phosphorylated Raf (p-Raf) protein were detected by Western blot.Results:The proliferation ability and metastasis rate of U251 cells in observation group were significantly lower than those in control group: (27.15 ± 1.38)% vs. (63.54 ± 2.47)% and (37.09 ± 3.74)% vs. (82.17 ± 9.24)%, the apoptosis rate of U251 cells was significantly higher than that in control group: (69.17 ± 5.83)% vs. (17.58 ± 1.22)%, and there were statistical differences ( P<0.01). The expression of total protein and VEGF, p-PI3K, p-Akt, p-Ras, p-Raf protein of U251 cells in observation group were significantly lower than those in control group (1.52 ± 0.23 vs. 2.39 ± 0.31, 0.73 ± 0.08 vs. 1.68 ± 0.45, 0.57 ± 0.11 vs. 1.89 ± 0.31, 0.68 ± 0.06 vs. 1.74 ± 0.51, 0.84 ± 0.12 vs. 1.99 ± 0.63 and 0.71 ± 0.08 vs. 1.52 ± 0.37), and there were statistical differences ( P<0.01). Conclusions:The lncRNA LBX2-AS1 is highly expressed in glioma cells. Silencing the expression of lncRNA LBX2-AS1 inhibits the proliferation and metastasis of glioma cells through EGFR pathway.

9.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 1529-1537, 2022.
Artigo em Chinês | WPRIM | ID: wpr-1015828

RESUMO

Statins can bring some benefits to the treatment of diabetic cardiomyopathy (DCM), but the specific molecular pathway of their action is still unclear. Recent studies have shown that abnormal expression of long noncoding RNA (lncRNA) is closely related to the pathological development of DCM. To compare the degree of myocardial injury between diabetic rats treated with rosuvastatin and rats treated with conventional therapy, the therapeutic pathway and potential target of rosuvastatin on DCM was investigated. Total RNA of DCM rats was extracted and 1ncRNA microarray was prepared to screen out differentially expressed 1ncRNA and bioinformatics analysis was carried out. The results showed that 770 target genes were up-regulated and 884 were down-regulated in the treatment group compared with the model group, which were mainly related to improvement of metabolic disorder, regulation of the ratio of myocardial cells to collagen fibers, reduction of myocardial injury and exercise burden, prevention of autonomic nervous system and microcirculation diseases and change of eating habits. The signaling pathways involved are mainly concentrated in sensory pathways, signal transduction, lipid metabolism and so on. It is suggested that rosuvastatin may play a role in the treatment of DCM by regulating the participation of 1ncRNA in glucose and lipid energy metabolism and ion balance, inhibiting the process of myocardial fibrosis and improving the effect of high glucose toxicity on autonomic nervous function.

10.
Acta Anatomica Sinica ; (6): 479-487, 2022.
Artigo em Chinês | WPRIM | ID: wpr-1015301

RESUMO

[Abstract] Objective To investigate whether levosimendan (Lev) affects hypoxia / reoxygenation (H / R) - induced cardiomyocyte proliferation, apoptosis and fibrosis by regulating the molecular axis of long chain noncoding RNA (LncRNA) eosinophil granule ontogeny transcript (EGOT) / microRNA (miR) -641. Methods Rat cardiomyocytes H9C2 were cultured in vitro, and H / R-treated cells were used to establish cell damage models, which were randomly divided into control group, H / R group, H / R + Lev 1 μmol / L (H / R + Lev-L) group, H / R + Lev 5 μmol / L (H / R + Lev-M) group, and H / R + Lev 10 μmol / L (H / R + Lev-H) group, 9 samples per group. MTT method was used to detect cell proliferation. Flow cytometry was used to detect the apoptosis rate. Real-time P CR was used to detect the expression levels of EGOT and miR-641 mRNA. P cDNA-EGOT and EGOT small interfering RNA (si-EGOT) were transfected into H9 C2 cells respectively, and the cell proliferation and apoptosis rates were detected by the above method. The dual luciferase report experiment verified the targeting relationship between EGOT and miR-641. Western blotting was used to detect the expression levels of Bax, Bcl-2, collagen I (colI), collagen Ⅲ (col Ⅲ), tissue inhibitor of matrix metalloproteinase 2 (TIMP 2), matrix metalloproteinase-2 (MMP -2) . Results Compared with the control group, the cell survival rate of the H / R group reduced significantly (P < 0. 05), the apoptosis rate increased significantly (P < 0. 05), and the protein levels of Bax, c I, col Ⅲ, TIMP 2, and MMP -2 increased significantly (P < 0. 05), the level of Bcl-2 protein reduced significantly (P < 0. 05), the expression level of EGOT reduced significantly (P < 0. 05), the expression level of miR-641 increased significantly (P < 0. 05) . Compared with the H / R group, the cell survival rate of the H / R + Lev-L group, H / R + Lev-M group, and H / R + Lev-H group increased significantly (P < 0. 05), and the apoptosis rate decreased significant (P < 0. 05), the protein levels of Bax, colI, colⅢ, TIMP 2, MMP -2 reduced significantly (P < 0. 05), the level of Bcl-2 protein increased significantly (P < 0. 05), the expression level of EGOT increased significantly (P < 0. 05), the expression level of miR-641 reduced significantly (P < 0. 05), and each index of H / R + Lev-L group, H / R + Lev-M group, H / R + Lev-H group, the difference was statistically significant (P < 0. 05) . The dual luciferase report experiment confirmed that EGOT ccould target and bind to miR-641. The effect of transfecting pcDNA-EGOT and Lev was similar. Transfection of si-EGOT could reduce the effect of Lev on H / R-induced proliferation, apoptosis and fibrosis of H9 C2 cells. Conclusion Levosimendan may promote H / R-induced H9 C2 cell proliferation and inhibit apoptosis and fibrosis by up-regulating EGOT expression and down-regulating miR-641 expression.

11.
Journal of Zhejiang University. Science. B ; (12): 502-514, 2022.
Artigo em Inglês | WPRIM | ID: wpr-939822

RESUMO

Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‍‒‍microRNA (miRNA)‍‒‍‍messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.


Assuntos
Animais , Ratos , Linhagem Celular Tumoral , Proliferação de Células , Hormônio Foliculoestimulante/metabolismo , Regulação Neoplásica da Expressão Gênica , Hibridização in Situ Fluorescente , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo
12.
Chinese Journal of Trauma ; (12): 72-79, 2021.
Artigo em Chinês | WPRIM | ID: wpr-909835

RESUMO

Objective:To explore the impact of the expression of long noncoding RNA-nuclear-enriched abundant transcript 1 (NEAT1) on neurological function and neuronal apoptosis after traumatic brain injury (TBI) in mice and the possible mechanism.Methods:According to the random number table, 90 C57BL/6J mice were divided into sham group, blank control group, empty virus group 1, empty virus group 2, NEAT1 over-expression group and NEAT1 knockdown group, with 15 mice per group. The traumatic brain injury (TBI) was simulated by controlled cortical injury (CCI) model, and NEAT1 was regulated by intracerebroventricular injection with recombinant adenovirus. The neurological severity score (NSS) and Morris water maze test were used to evaluate the neurological function in blank control group, NEAT1 over-expression group and NEAT1 knockdown group within 1 week and 14-21 days after injury. The Western blot was used to observe the expressions of P53-induced protein with a death domain 1 (Pidd1), caspase-2, caspase-9 and caspase-3 in blank control group at 6 hour and 1, 3, 7 days after injury. The TUNEL method and immunofluorescence were used to observe the neurological apoptosis and expression of Pidd1 in blank control group, NEAT1 over-expression group and NEAT1 knockdown group at 3 days after injury. The Western blot analysis was used to detect protein expressions of Pidd1, caspase-2, cytochrome c (Cyt c) and caspase-3 in sham group, blank control group, empty virus groups, NEAT1 over-expression group and NEAT1 knockdown group at 3 days after injury.Results:The NSS was significantly reduced in NEAT1 over-expression group [(3.5±0.7)points], and was significantly increased in NEAT1 knockdown group [(5.0±1.5)points]at day 1 after injury, when compared with blank control group [(4.9±1.0)points]( P<0.01). The Morris water maze test showed that the time to find platform was decreased in NEAT1 over-expression group[(10.9±2.8)seconds], and was prolonged in NEAT1 knockdown group [(30.7±6.2)seconds] at day 19 after injury ( P<0.05 or 0.01), when compared with blank control group [(20.1±5.6)seconds]. The Western blot analysis showed that the expressions of Pidd1, caspase-2, caspase-9 and caspase-3 had significant increase at day 3 after injury ( P<0.01). The TUNEL test showed that the apoptosis rate of neurons was significantly decreased in NEAT1 over-expression group [(18.0±2.7)%], and the apoptosis rate was significantly increased in NEAT1 knockdown group [(63.0±8.6)%] at day 3 after injury ( P<0.01). Immunofluorescence showed that the expression of Pidd1 protein in cytoplasm of the neurons was decreased in NEAT1 over-expression group [(22.7±2.2)%]( P<0.01), and was increased in NEAT1 knockdown group [(72.7±7.0)%]( P<0.01) at day 3 after injury, when compared with blank control group. The Western blot analysis showed that the expressions of Pidd1, capsase-2, Cyt c and caspase-3 were significantly reduced in NEAT1 over-expression group (0.5±0.0, 0.3±0.0, 0.5±0.0, 0.4±0.0) at day 3 after injury, when compared with blank control group. However, the results were opposite in NEAT1 knockdown group. Conclusion:After TBI, the NEAT1 can reduce the activation of caspase-3 through the Pidd1-caspase-2-Cyt c pathway after TBI, regulate neuronal apoptosis, and ultimately play a protective role in neurological function.

13.
Chinese Journal of Clinical Oncology ; (24): 757-762, 2021.
Artigo em Chinês | WPRIM | ID: wpr-861650

RESUMO

Objective: To investigate the miR-488-3p-mediated effects of the long-chain noncoding RNA (lncRNA) family with sequence similarity 201-member A (FAM201A) on the biological behavior and radiosensitivity of gastric cancer cells. Methods: Sixty-three pairs of gastric carcinoma tissues and paracancerous tissues were resected from gastric carcinoma patients, who underwent surgery (no radiotherapy or chemotherapy treatment before surgery) at Laiyang Central Hospital of Yantai City during January 2014 and January 2017. The expression levels of FAM201A and miR-488-3p in the 63 gastric cancer tissue samples and their paracancerous tissues were detected by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The gastric cancer cell line MGC803 with inhibited FAM201A expression was constructed. The proliferation and viability of MGC803 cells were assessed by the Methyl Thiazolyl Tetrazolium (MTT) assay; their apoptosis was measured by flow cytometry; and their migration and invasion abilities were tested by the Transwell assay. Further, the MGC803 cells were irradiated with different radiation intensities (0, 2, 4, 6, and 8 Gy). Cell survival fractions were measured by colony-formation assay, and cell survival curve was stimulated by the single-hit multi-target model. The dual-luciferase reporter gene assay and qRT-PCR were used to verify whether FAM201A targets miR-488-3p. Results: The expression level of FAM201A was significantly higher, while that of miR-488-3p was significantly lower in gastric cancer tissues than in the paracancerous tissues. Inhibiting FAM201A expression significantly suppressed the proliferation, migration, and invasion abilities of MGC803 cells, promoted their apoptosis, and increased their radiosensitivity. FAM201A negatively regulated miR-488-3p expression. Inhibiting miR-488-3p expression reversed the effects of the inhibition of FAM201A expression on the proliferation, apoptosis, migration, and radiosensitivity of MGC803 cells. Conclusions: Inhibiting the expression of the lncRNA FAM201A suppressed the proliferation, migration, and invasion abilities of gastric cancer cells, promoted their apoptosis, and increased their radiosensitivity by targeting miR-488-3p. Thus, FAM201A may serve as a novel molecular target for gastric cancer treatment.

14.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 15-21, 2021.
Artigo em Chinês | WPRIM | ID: wpr-906232

RESUMO

Objective:To investigate the mechanism of Xiangsha Liujunzi Tang in improving liver lipid deposition in ApoE<sup>-/-</sup> atherosclerotic (AS) mice by affecting long noncoding RNA-HC (Lnc-HC)/microRNA-130b (miR-130b) in the regulation of cholesterol metabolism. Method:Totolly 10 C57BL/6J mice were selected as normal controls, and 30 healthy ApoE<sup>-/-</sup> mice fed with high fat diet for 12 weeks were then randomly divided into the model group, Xiangsha Liujunzi Tang group(19.12 g·kg<sup>-1</sup>·d<sup>-1</sup>) and simvastatin group(2.275 mg·kg<sup>-1</sup>·d<sup>-1</sup>), with gavage administration for 4 weeks. The serum lipid level of mice was detected by automatic biochemistry analyzer, and the histopathological changes of liver cells were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect expression of long noncoding RNA-HC, and miR-130b. Real-time PCR and Western blot assay were used to detect gene and protein expression of peroxisome proliferator-activated receptor gamma (PPAR<italic>γ</italic>), liver X receptor (LXR), ATP-binding cassette transporters A1 (ABCA1), ATP-binding cassette transporters G1 (ABCG1), ATP-binding cassette transporters G5 (ABCG5), and ATP-binding cassette transporters G8 (ABCG8). Result:Compared with the normal control group, the mice in the model group showed abnormal blood lipids, larger liver cells, obvious fat vacuoles, significantly increased expression of Lnc-HC, miR-130b in liver, and significantly decreased gene and protein expression of PPAR<italic>γ</italic>, LXR, ABCA1, ABCG1, ABCG5, and ABCG8 in mice liver (<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the model group, the abnormal blood lipid levels of the mice in the Xiangsha Liujunzi Tang group and the simvastatin group were improved, and the number of fatty vacuoles of liver cells was significantly reduced, the expression of liver Lnc-HC, miR-130b in Xiangsha Liujunzi Tang group decreased significantly (<italic>P</italic><0.05,<italic>P</italic><0.01), the gene and protein levels of liver PPAR<italic>γ</italic>, ABCA1, ABCG1, ABCG5, ABCG8 in mice of the Xiangsha Liujunzi Tang group and the simvastatin group showed an upward trend. Among them, the gene and protein expression of LXR protein in the liver of the Xiangsha Liujunzi Tang group was significantly up-regulated (<italic>P</italic><0.05). Conclusion:Xiangsha Liujunzi Tang may improve the lipid deposition in the liver of ApoE<sup>-/- </sup>AS mice by affecting Lnc-HC/miR-130b to regulate the cholesterol metabolism process mediated by PPAR<italic>γ</italic>, thus playing a role in preventing and treating AS.

15.
Acta Pharmaceutica Sinica B ; (6): 340-354, 2021.
Artigo em Inglês | WPRIM | ID: wpr-881140

RESUMO

Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.

16.
Journal of Southern Medical University ; (12): 141-145, 2021.
Artigo em Chinês | WPRIM | ID: wpr-880841

RESUMO

OBJECTIVE@#To investigate the effects of overexpression of long noncoding RNA (lncRNA) MEG3 on the proliferation and invasion of glioblastoma U251 cells by suppressing the expression of hypoxia inducible factor 1@*METHODS@#The expression of lncRNA MEG3 and HIF1@*RESULTS@#The expression of MEG3 was significantly lower and HIF1@*CONCLUSIONS@#MEG3 overexpression inhibits the proliferation and invasion of U251 cells through suppressing the expression of HIF1


Assuntos
Humanos , Apoptose , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , MicroRNAs , RNA Longo não Codificante/genética
17.
Chinese Journal of Tissue Engineering Research ; (53): 2229-2234, 2021.
Artigo em Chinês | WPRIM | ID: wpr-848021

RESUMO

BACKGROUND: Long noncoding RNAs play a role In transcription and post-transcrlptlonal levels, participate in the regulation of bone regeneration, and are closely related to osteoarthritis as well.  OBJECTIVE: To review the research progress of long noncoding RNAs in bone regeneration and osteoarthritis. METHODS: A computer-based search of CNKI, PubMed, and Elsevier was performed for relevant articles regarding long noncoding RNAs in bone regeneration and osteoarthritis published from January 2000 to June 2019, including review, basic research and clinical research. The search terms were “LncRNA; bone; bone regeneration; osteoarthritis” in Chinese and English. After preliminarily reading titles and abstracts, irrelevant articles were excluded. According to the inclusion and exclusion criteria, 64 articles were finally included in result analysis. RESULTS AND CONCLUSION: Bone regeneration is a complex process involving the interaction of osteoblasts and osteoclasts. Long noncoding RNAs are involved in the differentiation of osteoblasts and the production of osteoclasts, which play an important role in the balance of osteoblasts and osteoclasts. Therefore, it is a key molecule of bone regeneration. Long noncoding RNAs are involved in the occurrence and development of osteoarthritis and differentially expressed in osteoarthritis patients and healthy people, some of which are elevated and some are decreased in osteoarthritis patients. Thus, defining their respective expression differences and functions is of great significance for the prevention and treatment of osteoarthritis.

18.
Chinese Journal of Biotechnology ; (12): 3933-3944, 2021.
Artigo em Chinês | WPRIM | ID: wpr-921477

RESUMO

Long noncoding RNAs (lncRNAs) are a class of RNA molecules that are greater than 200 nt in length and do not have protein-coding capabilities or encode micropeptides only. LncRNAs are involved in the regulation of cell proliferation, differentiation, apoptosis and other biological processes, and are closely associated with the occurrence, recurrence and metastasis of a variety of malignant hematologic diseases. This article summarizes the function, regulatory mechanism and potential clinical application of lncRNAs in leukemia. In general, lncRNAs regulate the occurrence and development of leukemia and the multi-drug resistance in chemotherapy through epigenetic modification, ribosomal RNA transcription, competitive binding with miRNA, modulating glucose metabolic pathway, and activating tumor-related signaling pathway. Studies on lncRNAs provide new references for understanding the pathogenesis of leukemia, uncovering new prognostic markers and potential therapeutic targets, and addressing the problems of drug resistance and post-treatment recurrence in patients in clinical treatment of leukemia.


Assuntos
Humanos , Proliferação de Células , Leucemia/genética , MicroRNAs , Neoplasias , RNA Longo não Codificante/genética
19.
Chinese Journal of Gastroenterology ; (12): 636-640, 2021.
Artigo em Chinês | WPRIM | ID: wpr-1016171

RESUMO

Long noncoding RNA (lncRNA) are defined as noncoding RNA with a length of more than 200 nucleotides, which can regulate a variety of cellular processes. LncRNA H19 is widely involved in the pathophysiological process of intestinal inflammation and intestinal cancer by regulating the function of intestinal mucosal barrier. This article reviewed the effect of lncRNA H19 on intestinal mucosal barrier under different intestinal states and inflammation-cancer related signaling pathway.

20.
International Journal of Biomedical Engineering ; (6): 486-490, 2021.
Artigo em Chinês | WPRIM | ID: wpr-929938

RESUMO

Cardiac hypertrophy is a common physiological or pathological process, and pathological cardiac hypertrophy can lead to heart failure, sudden death, etc. The role of microRNA (miRNA or MIR) in myocardial hypertrophy has gradually attracted public attention. miR-1 plays a certain protective role in the occurrence of cardiac hypertrophy. miR-133 is a key factor in the establishment of mast gene program, which is very important for the development of myocardial hypertrophy. Carvedilol and other drugs can regulate the expression of miR-133. miR-208a plays an important physiological role in the cardiovascular system, and its expression level changes dynamically in a variety of cardiovascular diseases such as cardiac hypertrophy, which is closely related to the progression and prognosis of the disease. The expression of miR-199a is up-regulated in pressure-overload cardiac hypertrophy, and it is found that miR-199a can inhibit autophagy of cardiomyocytes and induce the occurrence of cardiac hypertrophy. miR-200c can protect cardiomyocytes through a variety of pathways. miRNA may become an important biomarker or drug therapeutic target for cardiac hypertrophy. With the deepening of the research on non-coding RNAs including miRNA, its regulation on the occurrence of cardiac hypertrophy and the pathological process of heart failure will be further revealed.

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