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1.
Circ Res ; 134(4): 425-441, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38299365

RESUMO

BACKGROUND: Human cardiac long noncoding RNA (lncRNA) profiles in patients with dilated cardiomyopathy (DCM) were previously analyzed, and the long noncoding RNA CHKB (choline kinase beta) divergent transcript (CHKB-DT) levels were found to be mostly downregulated in the heart. In this study, the function of CHKB-DT in DCM was determined. METHODS: Long noncoding RNA expression levels in the human heart tissues were measured via quantitative reverse transcription-polymerase chain reaction and in situ hybridization assays. A CHKB-DT heterozygous or homozygous knockout mouse model was generated using the clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 system, and the adeno-associated virus with a cardiac-specific promoter was used to deliver the RNA in vivo. Sarcomere shortening was performed to assess the primary cardiomyocyte contractility. The Seahorse XF cell mitochondrial stress test was performed to determine the energy metabolism and ATP production. Furthermore, the underlying mechanisms were explored using quantitative proteomics, ribosome profiling, RNA antisense purification assays, mass spectrometry, RNA pull-down, luciferase assay, RNA-fluorescence in situ hybridization, and Western blotting. RESULTS: CHKB-DT levels were remarkably decreased in patients with DCM and mice with transverse aortic constriction-induced heart failure. Heterozygous knockout of CHKB-DT in cardiomyocytes caused cardiac dilation and dysfunction and reduced the contractility of primary cardiomyocytes. Moreover, CHKB-DT heterozygous knockout impaired mitochondrial function and decreased ATP production as well as cardiac energy metabolism. Mechanistically, ALDH2 (aldehyde dehydrogenase 2) was a direct target of CHKB-DT. CHKB-DT physically interacted with the mRNA of ALDH2 and fused in sarcoma (FUS) through the GGUG motif. CHKB-DT knockdown aggravated ALDH2 mRNA degradation and 4-HNE (4-hydroxy-2-nonenal) production, whereas overexpression of CHKB-DT reversed these molecular changes. Furthermore, restoring ALDH2 expression in CHKB-DT+/- mice alleviated cardiac dilation and dysfunction. CONCLUSIONS: CHKB-DT is significantly downregulated in DCM. CHKB-DT acts as an energy metabolism-associated long noncoding RNA and represents a promising therapeutic target against DCM.


Assuntos
Aldeído-Desidrogenase Mitocondrial , Cardiomiopatia Dilatada , RNA Longo não Codificante , Animais , Humanos , Camundongos , Trifosfato de Adenosina/metabolismo , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/metabolismo , Regulação para Baixo , Hibridização in Situ Fluorescente , Camundongos Knockout , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
2.
Circ Res ; 135(3): 434-449, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38864216

RESUMO

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 (nuclear factor of activated T cells/myocyte enhancer factor-2) pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1 (KRAB-associated protein-1). lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.


Assuntos
Cardiomegalia , Camundongos Knockout , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Cardiomegalia/metabolismo , Cardiomegalia/genética , Cardiomegalia/prevenção & controle , Cardiomegalia/patologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/prevenção & controle , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Remodelação Ventricular
3.
Circulation ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39005211

RESUMO

BACKGROUND: Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood. METHODS: Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called HEAT4 (heart failure-associated transcript 4). HEAT4 expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction, or cardiogenic shock. The transcriptional regulation of HEAT4 was verified through cytokine treatment and single-cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA-protein interaction assays uncovered a mechanistic role of HEAT4 in the monocyte anti-inflammatory gene program. HEAT4 expression and function was characterized in a vascular injury model in NOD.CB17-Prkdc scid/Rj mice. RESULTS: HEAT4 expression was increased in the blood of patients with HF, acute myocardial infarction, or cardiogenic shock. HEAT4 levels distinguished patients with HF from people without HF and predicted all-cause mortality in a cohort of patients with HF over 7 years of follow-up. Monocytes, particularly anti-inflammatory CD16+ monocytes, which are increased in patients with HF, are the primary source of HEAT4 expression in the blood. HEAT4 is transcriptionally activated by treatment with anti-inflammatory interleukin-10. HEAT4 activates anti-inflammatory and inhibits proinflammatory gene expression. Increased HEAT4 levels result in a shift toward more CD16+ monocytes. HEAT4 binds to S100A9, causing a monocyte subtype switch, thereby reducing inflammation. As a result, HEAT4 improves endothelial barrier integrity during inflammation and promotes vascular healing after injury in mice. CONCLUSIONS: These results characterize a novel endogenous anti-inflammatory pathway that involves the conversion of monocyte subtypes into anti-inflammatory CD16+ monocytes. The data identify a novel function for the class of long noncoding RNAs by preventing protein secretion and suggest long noncoding RNAs as potential targets for interventions in the field of cardioimmunology.

4.
Circulation ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38841852

RESUMO

BACKGROUND: Dilated cardiomyopathy is characterized by left ventricular dilation and continuous systolic dysfunction. Mitochondrial impairment is critical in dilated cardiomyopathy; however, the underlying mechanisms remain unclear. Here, we explored the cardioprotective role of a heart-enriched long noncoding RNA, the dilated cardiomyopathy repressive transcript (DCRT), in maintaining mitochondrial function. METHODS: The DCRT knockout (DCRT-/-) mice and DCRT knockout cells were developed using CRISPR-Cas9 technology. Cardiac-specific DCRT transgenic mice were generated using α-myosin heavy chain promoter. Chromatin coimmunoprecipitation, RNA immunoprecipitation, Western blot, and isoform sequencing were performed to investigate the underlying mechanisms. RESULTS: We found that the long noncoding RNA DCRT was highly enriched in the normal heart tissues and that its expression was significantly downregulated in the myocardium of patients with dilated cardiomyopathy. DCRT-/- mice spontaneously developed cardiac dysfunction and enlargement with mitochondrial impairment. DCRT transgene or overexpression with the recombinant adeno-associated virus system in mice attenuated cardiac dysfunction induced by transverse aortic constriction treatment. Mechanistically, DCRT inhibited the third exon skipping of NDUFS2 (NADH dehydrogenase ubiquinone iron-sulfur protein 2) by directly binding to PTBP1 (polypyrimidine tract binding protein 1) in the nucleus of cardiomyocytes. Skipping of the third exon of NDUFS2 induced mitochondrial dysfunction by competitively inhibiting mitochondrial complex I activity and binding to PRDX5 (peroxiredoxin 5) and suppressing its antioxidant activity. Furthermore, coenzyme Q10 partially alleviated mitochondrial dysfunction in cardiomyocytes caused by DCRT reduction. CONCLUSIONS: Our study revealed that the loss of DCRT contributed to PTBP1-mediated exon skipping of NDUFS2, thereby inducing cardiac mitochondrial dysfunction during dilated cardiomyopathy development, which could be partially treated with coenzyme Q10 supplementation.

5.
Circulation ; 149(15): 1205-1230, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38189150

RESUMO

BACKGROUND: The relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by ZFPM2) is observed in human ventricles during HF and causes HF in mice. METHODS: FOG2 expression was assessed in human atria. The effect of adult-specific FOG2 overexpression in the mouse heart was evaluated by whole animal electrophysiology, in vivo organ electrophysiology, cellular electrophysiology, calcium flux, mouse genetic interactions, gene expression, and genomic function, including a novel approach for defining functional transcription factor interactions based on overlapping effects on enhancer noncoding transcription. RESULTS: FOG2 is significantly upregulated in the human atria during HF. Adult cardiomyocyte-specific FOG2 overexpression in mice caused primary spontaneous AF before the development of HF or atrial remodeling. FOG2 overexpression generated arrhythmia substrate and trigger in cardiomyocytes, including calcium cycling defects. We found that FOG2 repressed atrial gene expression promoted by TBX5. FOG2 bound a subset of GATA4 and TBX5 co-bound genomic locations, defining a shared atrial gene regulatory network. FOG2 repressed TBX5-dependent transcription from a subset of co-bound enhancers, including a conserved enhancer at the Atp2a2 locus. Atrial rhythm abnormalities in mice caused by Tbx5 haploinsufficiency were rescued by Zfpm2 haploinsufficiency. CONCLUSIONS: Transcriptional changes in the atria observed in human HF directly antagonize the atrial rhythm gene regulatory network, providing a genomic link between HF and AF risk independent of atrial remodeling.


Assuntos
Fibrilação Atrial , Remodelamento Atrial , Insuficiência Cardíaca , Humanos , Camundongos , Animais , Fibrilação Atrial/genética , Redes Reguladoras de Genes , Cálcio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Átrios do Coração , Insuficiência Cardíaca/genética , Genômica , Fator de Transcrição GATA4/genética
6.
Mol Biol Rep ; 51(1): 270, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302810

RESUMO

Dementia is the term used to describe a group of cognitive disorders characterized by a decline in memory, thinking, and reasoning abilities that interfere with daily life activities. Examples of dementia include Alzheimer's Disease (AD), Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), Vascular dementia (VaD) and Progressive supranuclear palsy (PSP). AD is the most common form of dementia. The hallmark pathology of AD includes formation of ß-amyloid (Aß) oligomers and tau hyperphosphorylation in the brain, which induces neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Emerging studies have associated long non-coding RNAs (lncRNAs) with the pathogenesis and progression of the neurodegenerative diseases. LncRNAs are defined as RNAs longer than 200 nucleotides that lack the ability to encode functional proteins. LncRNAs play crucial roles in numerous biological functions for their ability to interact with different molecules, such as proteins and microRNAs, and subsequently regulate the expression of their target genes at transcriptional and post-transcriptional levels. In this narrative review, we report the function and mechanisms of action of lncRNAs found to be deregulated in different types of dementia, with the focus on AD. Finally, we discuss the emerging role of lncRNAs as biomarkers of dementias.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , RNA Longo não Codificante , Humanos , Doença de Alzheimer/genética , RNA Longo não Codificante/genética , Peptídeos beta-Amiloides
9.
Clin Exp Reprod Med ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853128

RESUMO

Objective: To investigate whether long non-coding RNA (lncRNA) Gm8097 (LncGm8097) is associated with male infertility. Methods: The expression and bilogical role of LncGm8097 were investigated. Results: LncGm8097 expression was down-regulated in the testis tissues with moderate and severe hypospermatogenesis compared with those with normal spermatogenesis and mild hypospermatogenesis (p<0.05). LncGm8097 down-regulation significantly promoted apoptosis and inhibited proliferation in GC1 and GC2 cells. In addition, LncGm8097 was significantly down-regulated in mouse model of hypospermatogenesis and correlated with cell apoptosis and proliferation. LncGm8097 was located immediately upstream of PRPS2, and correlated with Bcl-2/P53/caspase 6/caspase 9 signal pathway. Conclusion: LncGm8097 down-regulation correlates with hypospermatogenesis, which may offer new insights into the pathogenesis of male infertility.

10.
Taiwan J Obstet Gynecol ; 63(1): 46-56, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38216268

RESUMO

OBJECTIVE: Despite continuous progress in treatment, recurrence and metastasis limit further improvement in the prognosis of breast cancer (BC) patients. Our aim was to search for a crucial prognostic biomarker of BC. MATERIALS AND METHODS: Patient data were selected from The Cancer Genome Atlas (TCGA) and GTEx databases. Several online public databases, including Gene Expression Profiling Interactive Analysis (GEPIA), miRWalk, miRDB, and LncBase Predicted v.2, were used to identify potential upstream miRNAs and lncRNAs. These findings were validated through in vitro experiments. RESULTS: A total of 1, 097 invasive BC samples and 572 normal breast tissues (including 113 samples from TCGA and 459 samples from GTEx) were collected for the study. CCT4 was not only significantly overexpressed in BC compared with normal breast tissues but also had important prognostic significance (P < 0.001). By intersecting miRWalk and miRDB and conducting correlation analysis, hsa-miR-30c-2-3p was identified as the most probable upstream miRNA of CCT4. Following an extensive assessment that included survival analysis, correlation analysis, and common binding-site prediction, LINC01234 was chosen as the most likely upstream lncRNA. In vitro experiments showed that LINC01234-siRNA inhibited the proliferation, invasion, and migration abilities of BC cells. Western blot analysis further confirmed that LINC01234 promoted malignant behaviors of BC cells via the CCT4/mTOR signaling pathway. CONCLUSION: The LINC01234/hsa-miR-30c-2-3p/CCT4/mTOR axis was identified as a potential ceRNA regulatory mechanism in BC. These findings established the foundation for systematically unveiling the pathological mechanisms of BC and provided new insights for targeted therapy of BC patients.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , MicroRNAs/genética , Prognóstico , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Linhagem Celular Tumoral , Chaperonina com TCP-1/genética , Chaperonina com TCP-1/metabolismo
11.
Cancer Research and Clinic ; (6): 191-198, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1030434

RESUMO

Objective:To explore the expression of long non-coding RNA (lncRNA) RP13-349O20.2 in cervical cancer tissues and its impact on the migration, invasion abilities and chemotherapy sensitivity of cervical cancer cells in vitro and the possible mechanisms.Methods:The GEPIA.CANCER website (the data was updated in June 2023) was used to analyze the relationship between the expression level of RP13-349O20.2 and the overall survival of 253 cervical cancer patients. From January 2020 to August 2022, cancer tissues and paracancerous tissues (>2 cm from the tumor edge) from 40 cervical cancer patients in the Affiliated Tengzhou Central People's Hospital of Xuzhou Medical University were retrospectively collected. Human normal cervical epithelial cells H8 and human cervical cancer cell lines HCC94, C33A, Hela, HCC1106 and SiHa were used for cell experiments in vitro. Real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect the relative expression of RP13-349O20.2 in cervical cancer tissues, paracancerous tissues and each cell line. The C33A cells with the highest relative expression level of RP13-349O20.2 were transfected with small interfering RNA (siRNA) of RP13-349O20.2 and siRNA of its negative control sequence, and they were si-RP13-349O20.2 group and si-Con group, respectively. The scratch healing assay was used to detect the migration ability of C33A cells in the two groups, the Transwell assay was used to detect the invasion ability of C33A cells, and the CCK-8 method was used to detect the sensitivity of C33A cells to 5-fluorouracil. The absorbance value indicated the cell proliferation ability, the lower the absorbance value, the weaker the proliferation ability, the more sensitive to the drug. Dual-luciferase reporter gene assay was used to verify the targeting relationship between RP13-349O20.2 and miRNA-493-5p (miR-493-5p), miR-493-5p and Nectin-4. qRT-PCR was used to detect the relative expression of miR-493-5p and Nectin-4 mRNA in two groups of C33A cells, and Western blotting was used to detect the expressions of Nectin-4 protein and PI3K-AKT signaling pathway proteins in two groups of cells.Results:Analysis based on data from GEPIA.CANCER website shows that patients with low expression of RP13-349O20.2 had better overall survival than patients with high expression ( P < 0.01). The relative expression levels of RP13-349O20.2 in cervical cancer tissues and paracancerous tissues of 40 patients were 4.04±0.32 and 1.18±0.14, and the difference was statistically significant ( t = 8.29, P < 0.01). Compared with H8 cells, the expressions of RP13-349O20.2 in human cervical cancer cell lines HCC94, C33A, Hela, HCC1106 and SiHa were higher (all P < 0.01). The relative expression levels of RP13-349O20.2 in C33A cells in the si-Con group and si-RP13-349O20.2 group were 7.30±0.30 and 1.01±0.27, and the difference was statistically significant ( t = 15.62, P < 0.01). The scratch healing rates of C33A cells in the si-Con group and si-RP13-349O20.2 group were (32±9)% and (75±6)% ( t = 3.97, P < 0.01), and the numbers of invasive cells were (106±12) cells and (36±8) cells ( t = 4.79, P < 0.01). After the action of 5, 10, 20, 40 and 80 μmol/L 5-fluorouracil for 24 h, the absorbance value of C33A cells in the si-RP13-349O20.2 group was lower than that in the si-Con group. Dual-luciferase reporter gene assay confirmed that there was a targeting relationship between P13-349O20.2 and miR-493-5p ( P < 0.01), and there was a targeting relationship between miR-493-5p and Nectin-4 ( P < 0.01) . The relative expression levels of miR-493-5p in C33A cells in the si-Con group and si-RP13-349O20.2 group was 1.02±0.13 and 5.48±0.85 ( t = 5.21, P < 0.01). The relative expression levels of Nectin-4 mRNA were 5.65±0.33 and 0.99±0.34 ( t = 9.87, P < 0.01). The expression of Nectin-4 protein in C33A cells in the si-RP13-349O20.2 group was lower than that in the si-Con group ( t = 9.21, P = 0.001), and the expressions of PI3K-AKT signaling pathway proteins p-STAT3, p-PI3K, p-AKT and p-mTOR were lower than those in the si-Con group (all P < 0.01). Conclusions:The level of RP13-349O20.2 in cervical cancer tissues is high, and its high expression may indicate the poor prognosis of patients. Interfering with the expression of RP13-349O20.2 in vitro can inhibit the migration and invasion abilities of cervical cancer cells and promote the sensitivity of cervical cancer cells to 5-fluorouracil. The mechanism may be related to the miR-493-5p/Nectin-4 signaling pathway and the PI3K-AKT signaling pathway.

12.
Artigo em Chinês | WPRIM | ID: wpr-1018132

RESUMO

Long non-coding RNA (lncRNA) is a class of highly conserved transcript with a length of more than 200 nucleotides, which is of great significance for the occurrence, development, diagnosis and treatment of malignant tumors. The abnormal expression of linc01410 in malignant tumors can affect the occurrence and development of malignant tumors by regulating the biological processes such as proliferation, migration and epithelial-mesenchymal transformation of malignant tumor cells, acting on related signaling pathways such as nuclear factor-κB and Notch or through exosome pathways.

13.
Artigo em Chinês | WPRIM | ID: wpr-1027525

RESUMO

Objective:To investigate the expression of long non-coding RNA 00665 (LINC00665) in hepatocellular carcinoma (HCC) and its regulatory effect on angiogenesis of hepatocellular carcinoma cells and its potential molecular mechanism.Methods:HCC tissues and corresponding paracancerous tissues of 100 patients with HCC in the First Affiliated Hospital of Nanjing Medical University from May 2016 to April 2017 were collected, and the survival prognosis was compared. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of LINC00665 in HCC tissues and cells. The effect of LINC00665 overexpressed Hep-3B cells on the angiogenesis of human umbilical vein endothelial cells (HUVEC) was examined by tube formation assay and chick chorioallantoic membrane assay. Bioinformatics database predicted the downstream microRNA (miRNA) and target genes of LINC00665, and the relationship between LINC00665, miR-126-5p and vascular endothelial growth factor A (VEGFA) was verified by RT-qPCR, Western blot and dual-luciferase reporter gene assay.Results:The expression level of LINC00665 in HCC (6.5±2.8) was significantly higher than that in paracancer tissues (4.8±3.1), the difference was statistically significant ( t=4.12, P<0.001). According to the median LINC00665 expression level of 100 patients with HCC, the cumulative survival rate of LINC00665 high expression group ( n=50) was lower than that of LINC00665 low expression group ( n=50), and the difference was statistically significant (χ 2=3.79, P=0.008). After co-culture with LINC00665 group (Hep-3B cells overexpressing LINC00665), the length of HUVEC cell tubule formation was (596.0±22.3) μm, and the number of HUVEC cell tubules was (36.3±4.5), which were both higher than NC group with the tubule formation length (127.0±13.5) μm and the number (9.3±1.5) of HUVEC cells co-cultured with Hep-3B cells of control group, and the differences were statistically significant ( t=31.15, 9.82, P<0.001, P=0.001). The chick chorioallantoic membrane assay results were similar to tube formation assay. Western blot detected that the relative expression of VEGFA in LINC00665 group was higher than that in NC group, the difference was statistically significant ( t=7.15, P<0.001). StarBase and DIANA database were used to predict and screen LINC00665 downstream miR-126-5p. StarBase database was used to predict the binding sites of LINC00665/miR-126-5p/VEGFA axis. In dual-luciferase reporter gene assay, the fluorescence intensity of LINC00665 and VEGFA vector co-transfected with miR-126-5p mimics decreased. Conclusion:LINC00665 is highly expressed in HCC and is associated with poor prognosis in patients with HCC. LINC00665 promotes angiogenesis of HCC by regulating the miR-126-5p/VEGFA axis.

14.
Artigo em Chinês | WPRIM | ID: wpr-1018146

RESUMO

Long non-coding RNA (lncRNA) is an RNA molecule that does not code to express proteins, and plays an important role in the occurrence and development of a variety of tumors. As an lncRNA, SPRY4-IT1 is highly expressed in breast cancer tissues, and can be used as an upstream and downstream regulator of breast cancer, promoting the progression of breast cancer, and is closely related to breast cancer stage and prognosis. In-depth study of the molecular mechanism associated with SPRY4-IT1 and breast cancer can provide new ideas for discovering biomarkers for early diagnosis of breast cancer, assessing disease prognosis and finding targeting sites.

15.
Journal of Chinese Physician ; (12): 1845-1848, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1026044

RESUMO

Objective:To investigate the effect of long chain non coding RNA (LncRNA)-myocardial infarction associated transcript (MIAT) mediated expression of microRNA-205 (miR-205) on acute kidney injury in septic rats.Methods:A total of 32 clean grade Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, a transfection control group, and a transfection group, with 8 rats in each group. Except for the normal group, other groups of rats were used to establish sepsis acute kidney injury models by cecal ligation and puncture method. The control group was transfected with non-specific small interfering RNA (siRNA), while the transfection group was transfected with LncRNA-MIAT specific siRNA. The expression of miR-205 in renal tissue was measured using real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method; The serum levels of creatinine (Scr) and urea nitrogen (BUN) were measured using a fully automated biochemical analyzer; The levels of serum interleukin-6 (IL-6) and tumor necrosis factor -α (TNF -α) were measured using enzyme-linked immunosorbent assay (ELISA); In situ end labeling (TUNEL) method was used to determine apoptosis in rat kidney tissue cells.Results:Compared with the normal group, the model group, transfected control group, and transfected group had higher relative expression levels of miR-205 (all P<0.05); The relative expression level of miR-205 in the transfection group was lower than that in the model group and transfection control group (all P<0.05). Compared with the normal group, the model group, transfection control group, and transfection group had higher serum Scr and BUN levels (all P<0.05); The serum Scr and BUN levels in the transfection group were lower than those in the model group and transfection control group (all P<0.05). Compared with the normal group, the model group, transfection control group, and transfection group had higher levels of serum IL-6 and TNF -α (all P<0.05); The serum IL-6 and TNF-α levels in the transfection group were lower than those in the model group and the transfection control group (all P<0.05). Compared with the normal group, the model group, transfection control group, and transfection group had higher rates of renal tissue cell apoptosis (all P<0.05); The apoptosis rate of renal tissue cells in the transfection group was lower than that in the model group and transfection control group (all P<0.05). Conclusions:LncRNA-MIAT exerts a renal protective effect on acute kidney injury in septic rats by regulating the expression of miR-205. Its mechanism may be related to downregulating miR-205 expression, reducing inflammatory response, and reducing cell apoptosis in renal tissue.

16.
Journal of Chinese Physician ; (12): 1917-1920, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1026051

RESUMO

Long chain non coding RNA (LncRNA) is widely involved in various biological processes such as intracellular chromatin modification, transcriptional regulation, nuclear transport, and protein function regulation, and is closely related to various key physiological functions such as immunity and metabolism in the body. NEAT1 (nuclear parapackle assembly transcript 1) is a newly discovered LncRNA, which is an important component of the nuclear substructural paraplaques. It has been proven to regulate downstream protein expression by binding to various miRNAs, thereby regulating the expression of inflammatory factors, epithelial mesenchymal transition, autophagy, apoptosis, proliferation, migration, and other biological processes, Its abnormal expression plays an important role in the pathogenesis of lung diseases such as asthma, chronic obstructive pulmonary disease, pneumonia, pulmonary fibrosis, and lung cancer, and is closely related to the prognosis of non-small cell lung cancer and the sensitivity of anti-tumor drugs. It is expected to become a new biological marker and therapeutic intervention target. This article mainly reviews the latest research progress on the role of NEAT1 in lung diseases.

17.
Artigo em Chinês | WPRIM | ID: wpr-989520

RESUMO

Osteosarcoma is the most common primary solid bone malignancy. The main factor leading to recurrence and metastasis of osteosarcoma is resistance to chemotherapy drugs. Long non-coding RNAs can affect drug resistance in osteosarcoma by regulating epithelial-mesenchymal transition, cell autophagy, apoptosis, drug efflux, and cell cycle, suggesting that long non-coding RNAs may become new targets for drug resistance in osteosarcoma treatment.

18.
Artigo em Chinês | WPRIM | ID: wpr-989544

RESUMO

Objective:To investigate the regulatory effect of long non-coding RNA (lncRNA) FTX on gastric cancer cell proliferation through miR-22-3p/NOD-like receptor protein 3 (NLRP3) inflammasome pathway.Methods:The gastric cancer cell line NCI-N87 were divided into blank control group, si-FTX-NC group, si-FTX group, si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group. Quantitative real-time fluorescent PCR was performed to analyze the expression levels of lncRNA FTX and miR-22-3p, clone formation assay was performed to analyze the proliferation ability of NCI-N87 cells, western blotting was performed to analyze the expressions of NLRP3 inflammasome pathway proteins, and dual-luciferase reporter assay was performed to analyze the targeting relationship between lncRNA FTX and miR-22-3p.Results:The relative expressions of lncRNA FTX in the blank control group, si-FTX-NC group, si-FTX group, si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group were 1.03±0.09, 1.01±0.15, 0.42±0.08, 0.45±0.06 and 0.46±0.13 respectively, with a statistically significant difference ( F=52.19, P<0.001). The relative expressions of miR-22-3p were 1.04±0.12, 0.97±0.08, 2.26±0.15, 2.23±0.13 and 1.15±0.11 respectively, with a statistically significant difference ( F=178.53, P<0.001). Compared with the blank control group and si-FTX-NC group, the relative expressions of lncRNA FTX in the si-FTX group, si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group decreased (all P<0.001). Compared with the blank control group, si-FTX-NC group and si-FTX+miR-22-3p inhibitor group, the relative expressions of miR-22-3p in the si-FTX group and si-FTX+miR-22-3p inhibitor-NC group increased (all P<0.001). The clones of the five groups were 115.50±7.25, 112.33±8.46, 54.83±5.17, 56.17±6.32 and 85.67±9.43, with a statistically significant difference ( F=91.67, P<0.001). The levels of NLRP3 protein in the five groups were 1.84±0.17, 1.86±0.12, 0.95±0.09, 0.97±0.11 and 1.28±0.19, with a statistically significant difference ( F=60.62, P<0.001). Compared with the blank control group and si-FTX-NC group, the number of clones and the level of NLRP3 protein of the si-FTX group, si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group decreased (all P<0.05). Compared with the si-FTX+miR-22-3p inhibitor group, the number of clones and the level of NLRP3 protein in the si-FTX group and si-FTX+miR-22-3p inhibitor-NC group decreased (all P<0.05). The dual-luciferase reporter assay found that miR-22-3p was the target gene of lncRNA FTX. Conclusion:Silencing the expression of lncRNA FTX can inhibit the proliferation of gastric cancer cells, and the mechanism may be related to the regulation of lncRNA FTX on the miR-22-3p/NLRP3 inflammasome pathway.

19.
Cancer Research and Clinic ; (6): 808-814, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1030377

RESUMO

Objective:To construct a prognostic risk model of bladder cancer using cuproptosis-associated long non-coding RNA (lncRNA) and test its predictive efficacy.Methods:RNA expression sequencing data and clinical data of corresponding samples were downloaded from The Cancer Gene Atlas (TCGA) database. The 17 key genes associated with cuproptosis was obtained from the published literature, and then lncRNA of the key genes associated with cuproptosis was screened by correlation analysis based on the lncRNA data from TCGA database. The cuproptosis lncRNA associated with the prognosis of bladder cancer patients were screened by using Cox regression and Lasso regression. A total of 403 bladder cancer patients with complete clinical information screened from TCGA database were divided into a training set (203 cases) and a test set (200 cases), and the prognostic risk prediction model was constructed based on the samples in the training set and the above key independent prognosis-related cuproptosis lncRNA. According to the median value of the risk score, patients in all the datasets, the test set and the training set of bladder cancer screened from TCGA database were divided into high-risk group and low-risk group, and R language survival package was applied to compare the differences in overall survival between the two groups in each dataset. The predictive effect of the model was verified using principal component analysis (PCA) and receiver operating characteristic (ROC) curve. Univariate and multivariate Cox regression analysis were used to analyze the factors affecting overall survival of 403 bladder cancer patients, and ROC curve was used to analyze the efficacy of each factor for predicting the prognosis of bladder cancer.Results:After screening, a total of 4 cuproptosis lncRNA with independent prognostic significance were included (AC104564.3, LINC00649, AL136084.3 and AL136295.2), and the prognostic model constructed based on these 4 lncRNA was as follows: risk score = -0.713 42×AC104564.3-0.744 94×LINC00649+0.410 93×AL136084.3-0.736 89×AL136295.2. Survival analysis showed that the overall survival of the high-risk group in all datasets, the test set and the training set was poorer than that of the low-risk group (all P < 0.05), suggesting that a high risk score predicted poor prognosis. ROC curve analysis showed that the areas under the curve of applying the risk prediction model to predict 1-, 3- and 5-year overall survival of all 403 patients in TCGA database were 0.665, 0.629 and 0.692. Multivariate Cox regression analysis showed that age (≥ 65 years old vs. < 65 years old: OR = 1.027, 95% CI 1.011-1.044, P < 0.001), stage (stage Ⅳ vs. stage Ⅲ vs. stage Ⅱ vs. stage Ⅰ vs. unknown stage: OR = 1.593, 95% CI 1.308-1.939, P < 0.001) and risk score (high vs. low: OR = 1.258, 95% CI 1.126-1.406, P < 0.001) were the independent influencing factors of patients' overall survival. ROC curve analysis showed that the areas under the curve of age, stage and risk score for predicting the patients' 5-year overall survival were 0.614, 0.685 and 0.692, suggesting that the risk prediction model had better predictive efficacy. Conclusions:A prognosis risk prediction model for bladder cancer patients is constructed based on 4 lncRNA associated with cuproptosis, and the model is internally validated to have a high predictive efficacy.

20.
Artigo em Chinês | WPRIM | ID: wpr-989538

RESUMO

E2F1, a nucleoprotein gene belongs to transcription factor, is closely associated with the development of malignant tumours. Long non-coding RNAs (lncRNAs) are aberrantly expressed in a variety of tumors. In studies of molecular mechanisms associated with lncRNAs and tumours, E2F1 has been identified as a key factor that can play a critical role as an upstream regulator or downstream target of lncRNAs, and even inter-regulate to form a positive feedback loop. This paper reviews the significance of the interaction between E2F1 and lncRNA in malignant tumors in recent years, and aims to provide ideas for the study of tumor mechanisms.

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