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1.
Cell ; 184(7): 1790-1803.e17, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33735607

RESUMO

The long non-coding RNA (lncRNA) XIST establishes X chromosome inactivation (XCI) in female cells in early development and thereafter is thought to be largely dispensable. Here, we show XIST is continually required in adult human B cells to silence a subset of X-linked immune genes such as TLR7. XIST-dependent genes lack promoter DNA methylation and require continual XIST-dependent histone deacetylation. XIST RNA-directed proteomics and CRISPRi screen reveal distinctive somatic cell-type-specific XIST complexes and identify TRIM28 that mediates Pol II pausing at promoters of X-linked genes in B cells. Single-cell transcriptome data of female patients with either systemic lupus erythematosus or COVID-19 infection revealed XIST dysregulation, reflected by escape of XIST-dependent genes, in CD11c+ atypical memory B cells (ABCs). XIST inactivation with TLR7 agonism suffices to promote isotype-switched ABCs. These results indicate cell-type-specific diversification and function for lncRNA-protein complexes and suggest expanded roles for XIST in sex-differences in biology and medicine.


Assuntos
Linfócitos B/imunologia , Lúpus Eritematoso Sistêmico , RNA Longo não Codificante/fisiologia , Receptor 7 Toll-Like/imunologia , Inativação do Cromossomo X , /genética , Linhagem Celular , Metilação de DNA , Feminino , Inativação Gênica , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia
2.
BMC Cancer ; 21(1): 255, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750326

RESUMO

BACKGROUND: Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis. METHODS: RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm. RESULTS: A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types. CONCLUSIONS: MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma.


Assuntos
Neoplasias Colorretais/genética , MicroRNAs/fisiologia , Proteínas do Tecido Nervoso/fisiologia , RNA Longo não Codificante/fisiologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Imuno-Histoquímica , MicroRNAs/análise , Prognóstico , Mapas de Interação de Proteínas , RNA Longo não Codificante/análise , RNA Mensageiro/análise , RNA Mensageiro/fisiologia , Microambiente Tumoral
3.
Life Sci ; 275: 119288, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667514

RESUMO

AIMS: Hepatocellular carcinoma (HCC) is a malignant cancer that threatened human life seriously. Long non-coding RNA (lncRNA) BACE1-AS has been reported as a key regulator in tumorigenesis. Yet the specific correlation between BACE1-AS and HCC still needs further investigation. The primary purpose of our study is to reveal the exact correlation between BACE1-AS and HCC. MAIN METHODS: Bioinformatics via TCGA database revealed BACE1-AS closely related with HCC. qRT-PCR confirmed the abnormal BACE1-AS level in HCC tissues and cells. Databases prediction suggested that miR-377-3p might be a modulatory target of BACE1-AS and luciferase assay confirmed this hypothesis. Further study discovered that CELF1 also partook in the regulatory axis of BACE1-AS/miR-377-3p. Wound healing assays and transwell assays were utilized to investigate the impact of BACE1-AS, miR-377-3p and CELF1 in vitro. In vivo metastasis was examined by pulmonary metastasis model. KEY FINDINGS: This study found that BACE1-AS was overexpressed in HCC tissues and cell lines. Knockdown of BACE1-AS could restrain HCC progression in vitro, and inhibit pulmonary metastasis in vivo. MiR-377-3p was negatively modulated by BACE1-AS in HCC tumor tissues and cells. MiR-377-3p up-regulation inhibited HCC cells migration and invasion via inactivating EMT process. Moreover, CELF1 was identified as a downstream regulator of miR-377-3p and served as an oncogene in HCC cells. SIGNIFICANCE: Our findings supported that lncRNA BACE1-AS was up-regulated in HCC, promoting invasion and metastasis of hepatocellular carcinoma cells by modulating miR-377-3p/CELF1 axis via contributing to EMT pathway. BACE1-AS could be a potential biomarker in HCC for future treatment.


Assuntos
Proteínas CELF1/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Western Blotting , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Invasividade Neoplásica , Transplante de Neoplasias , RNA Longo não Codificante/fisiologia , Reação em Cadeia da Polimerase em Tempo Real
4.
BMC Cancer ; 21(1): 187, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622275

RESUMO

BACKGROUND: Super-enhancer-associated long noncoding RNAs (SE-lncRNAs) have been reported to play essential roles in tumorigenesis, but the fundamental mechanism of SE-lncRNAs in colorectal cancer (CRC) remains largely unknown. METHODS: A microarray was performed to identify the differentially expressed SE-lncRNAs between CRC tissues and peritumoral tissues. A novel SE-lncRNA, AC005592.2, was selected from these differentially expressed SE-lncRNAs to explore its effects on CRC development. Fluorescence quantitative real-time PCR (qRT-PCR) was used to assay the expression of AC005592.2 in CRC tissues and cell lines. Functional assays were applied to identify the biological effects of AC005592.2 in CRC cells. Furthermore, RNA-seq was employed to predict potential targets of AC005592.2. RESULTS: AC005592.2 was significantly increased in CRC tissues and cells. High expression of AC005592.2 was significantly associated with TNM stage and tumor differentiation in CRC patients. Knockdown of AC005592.2 suppressed CRC cell proliferation, invasion and migration but promoted apoptosis, while AC005592.2 overexpression exerted the opposite effects on CRC cells. In addition, AC005592.2 positively regulated the expression of olfactomedin 4 (OLFM4), which was also upregulated in CRC tissues. CONCLUSION: The findings suggested that AC005592.2 is a crucial promoter of CRC progression and may serve as an attractive therapeutic target for CRC.


Assuntos
Neoplasias Colorretais/patologia , Elementos Facilitadores Genéticos/fisiologia , Regulação Neoplásica da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/genética , RNA Longo não Codificante/fisiologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/genética , Progressão da Doença , Humanos , Invasividade Neoplásica , RNA Mensageiro/análise
5.
Mol Med Rep ; 23(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33325535

RESUMO

Burkitt lymphoma (BL) has a high mortality rate and its treatment is currently limited to chemotherapy combined with immunotherapy. The long non­coding RNA antisense non­coding RNA in the INK4 locus (ANRIL) has been identified as an oncogene that can regulate cell proliferation and apoptosis in multiple types of cancer. However, the function of ANRIL in BL remains unknown. The present study aimed to determine the effect of ANRIL on cell proliferation and apoptosis in BL. Reverse transcription­quantitative PCR was used to analyze the expression levels of ANRIL in BL cells. The effect of ANRIL knockdown on BL cells was determined using Cell Counting Kit­8, flow cytometric, western blotting, immunofluorescence staining and Hoechst staining assays. The results revealed that ANRIL silencing inhibited the proliferation and promoted the apoptosis of BL cells. In addition, the expression levels of cyclin D1, E2F transcription factor 1 and Bcl­2 were downregulated, while the expression levels of cyclin­dependent kinase inhibitor 1A, Bcl­2­associated X protein, cleaved­caspase­9/pro­caspase­9 and cleaved­caspase­3/pro­caspase­3 were upregulated. Furthermore, the knockdown of ANRIL activated the TGF­ß1 signaling pathway, as evidenced by the upregulated expression levels of TGF­ß1, phosphorylated (p)­SMAD2/3/SMAD2/3, p­SMAD1/SMAD1 and sphingosine­1­phosphate receptor 2. Moreover, the protective effect of ANRIL silencing in BL could be inhibited by the TGF­ß receptor type I/II dual inhibitor, LY2109761. In conclusion, the findings of the present study suggested that the knockdown of ANRIL may inhibit cell proliferation and promote cell apoptosis in BL by regulating the TGF­ß1 signaling pathway, which may provide a novel target for the treatment of BL.


Assuntos
Apoptose , Linfoma de Burkitt/genética , Proliferação de Células , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/fisiopatologia , Linhagem Celular Tumoral , Ciclina D1/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Fator de Transcrição E2F1/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Fator de Crescimento Transformador beta1/genética , Proteína X Associada a bcl-2/genética
6.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33215214

RESUMO

Long non­coding RNAs (lncRNAs) serve important roles in the tumorigenesis of a diverse range of cancer types. The lung cancer­associated transcript 1 (LUCAT1), has been reported to promote the proliferation, migration and invasion of oral squamous cell carcinoma cells. However, the exact role of LUCAT1 in laryngeal squamous cell carcinoma (LSCC) remains to fully understood. The present study aimed to interrogate the role and modulatory mechanism of LUCAT1 in LSCC. Reverse transcription­quantitative PCR and western blotting were used to investigate the expression of LUCAT1 and miR­493, as well as the protein expression of cyclin­dependent kinase 2, cyclin E1, p21, matrix metalloproteinase (MMP)2, MMP9, vascular endothelial growth factor­C, Bcl­2, Bax, cleaved caspase­3 and procaspase­3. Cell Counting Kit­8, flow cytometry, wound healing and Transwell assays were performed to analyze the proliferation, cell cycle, apoptosis levels, and the migratory and invasive abilities, respectively, of the LSCC AMC­HN­8 cell line. In addition, dual­luciferase reporter and ribonucleoprotein immunoprecipitation assays were used to investigate the binding between LUCAT1 and microRNA (miR)­493. The results of the present study revealed that the expression levels of LUCAT1 were upregulated in AMC­HN­8 cells. The genetic knockdown of LUCAT1 expression levels significantly suppressed the cell proliferation, alongside downregulating the expression levels of CDK2 and cyclin E1 and upregulating p21 expression levels. In addition, the knockdown of LUCAT1 inhibited cell migration and invasion, as demonstrated using the wound healing and Transwell assays, respectively. Moreover, LUCAT1 knockdown promoted cell apoptosis and upregulated the expression levels of Bax and cleaved caspase­3, whilst downregulating the expression levels of Bcl­2. Furthermore, LUCAT1 was discovered to directly bind to and inhibit the well­known tumor suppressor, miR­493. Notably, the specific inhibition of miR­493 partly blocked the anticancer effects of LUCAT1 knockdown in AMC­HN­8 cells. In conclusion, these results suggested that LUCAT1 may facilitate tumorigenesis in LSCC through the targeted inhibition of miR­493, which provides evidence for a novel target for the treatment of LSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , MicroRNAs/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Apoptose/genética , Caspase 3/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/fisiologia , Regulação para Cima , Fator C de Crescimento do Endotélio Vascular , Proteína X Associada a bcl-2/metabolismo
7.
Shanghai Kou Qiang Yi Xue ; 29(3): 267-274, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-33043343

RESUMO

PURPOSE: To investigate the molecular mechanism of LncRNA NEAT1 regulating proliferation, migration and invasion of tongue squamous cell carcinoma cells by regulating miR-339-5p/ITGA3 axis. METHODS: qRT-PCR and Western blot were used to detect the expression of NEAT1, miR-339-5p, ITGA3 mRNA and ITGA3 protein in 25 cases of human tongue squamous cell carcinoma, its corresponding adjacent tissues, human normal oral mucosal cell line HOK and human tongue squamous cell carcinoma cell lines TSCCA, CAL27, SCC15 and HN13. CAL27 cell lines that inhibited NEAT1 and overexpressed miR-339-5p were constructed, respectively. Cell viability was detected by MTT assay, cell numbers of migration and invasion were detected by Transwell assay, and the expression of Cyclin D1 and MMP-9 proteins were detected by Western blotting. The dual luciferase reporter gene was used to verify the targeting relationship of NEAT1, miR-339-5p and ITGA3, and the regulatory relationship was detected by Western blotting and qRT-PCR. SPSS 17.0 software package was used for statistical analysis of the data. RESULTS: Compared with normal human oral mucosal cell line HOK, the expression of NEAT1 and ITGA3 was up-regulated, while the expression of miR-339-5p was down-regulated in human tongue squamous cell carcinoma cell lines. Inhibition of NEAT1 or over-expression of miR-339-5p significantly inhibited proliferation, migration and invasion of CAL27 cells, and significantly inhibited expression of Cyclin D1 and MMP-9 proteins. Dual luciferase reporter gene assay confirmed that NEAT1 directly interacted with miR-339-5p and suppressed its expression. miR-339-5p negatively regulated ITGA3 expression. Inhibition of NEAT1 reversed the inhibitory effect of the inhibition of miR-339-5p on proliferation, migration and invasion of CAL27 cells. CONCLUSIONS: LncRNA NEAT1 promotes proliferation, migration and invasion of tongue squamous cell carcinoma cells by down-regulating miR-339-5p/ITGA3 axis.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , RNA Longo não Codificante/fisiologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina alfa3 , MicroRNAs/genética , RNA Longo não Codificante/genética
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1127-1135, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051429

RESUMO

Long non-coding RNA (lncRNA) have been attracted attention due to its role in many diseases. Taurine up-regulated gene 1(TUG1)is a non-coding RNA of 7.1 kb in length, which locates on chromosome 22q12. More and more studies have found that TUG1 not only participates in the occurrence and development of tumors, but also plays an important role in the progression of diseases in cardiovascular system, endocrine system, nervous system and so on. It is expected to become the therapeutic targets and indicators for evaluating prognosis of a variety of diseases such as diabetes, myocardial ischemia, osteoarthritis, atherosclerosis and so on.


Assuntos
Aterosclerose , MicroRNAs , RNA Longo não Codificante , Humanos , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Taurina
9.
Biol Res ; 53(1): 49, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092644

RESUMO

BACKGROUND: Although OIP5-AS1 has been characterized as an oncogenic lncRNA in many types of cancer, its role and underlying mechanism in ovarian carcinoma (OC) remains unknown. This study aimed to investigate the role of OIP5-AS1 in OC. METHODS: OC tissues and non-tumor tissues (ovary tissues within 3 cm around tumors) were collected from 58 OC patients (age range 36 to 67 years old, mean age 51.4 ± 5.9 years old). The expression of OIP5-AS1 and snail in paired tissues were determined by RT-qPCR. The interaction between OIP5-AS1 and miR-34a was predicted by IntaRNA2.0 and confirmed by dual luciferase reporter assay. The effects of overexpression of OIP5-AS1 and miR-34a on the expression of snail were analyzed by RT-qPCR and Western blotting. Cell invasion and migration were analyzed by Transwell assay. RESULTS: We observed that the expression of OIP5-AS1 and snail was upregulated and positively correlated with each other in OC. RNA-RNA interaction analysis showed that OIP5-AS1 might sponge miR-34a. In OC cells, overexpression of OIP5-AS1 resulted in the upregulated expression of snail, while overexpression of miR-34a downregulated the expression of snail. In addition, overexpression of miR-34a reduced the effects of overexpression of OIP5-AS1 on the expression of snail. In cell invasion and migration assay, overexpression of OIP5-AS1 and snail resulted in increased OC cell invasion and migration, while overexpression of miR-34a decreased OC cell invasion and migration. Moreover, overexpression of miR-34a attenuated the effects of OIP5-AS1 overexpression on OC cell invasion and migration. CONCLUSIONS: Therefore, OIP5-AS1 may upregulate snail expression in OC by sponging miR-34a to promote OC cell invasion and migration.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Adulto , Idoso , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia
10.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(5): 550-557, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-33085241

RESUMO

OBJECTIVE: To investigate the mechanism underlying the regulation of the invasion and metastasis of oral squamous cell carcinoma (OSCC) by long-chain noncoding RNA (lncRNA) PCGEM1 through the transforming growth factor (TGF) ß2/Smad2 signaling pathways. METHODS: A total of 60 OSCC cases were collected. Cancer tissues and normal tissues more than 2 cm away from cancer tissues were also collected. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-148a and lncRNA PCGEM1 in OSCC, adjacent normal tissues, oral mucosa epithelial cells, KB, BcaCD885, SCC-4, CAL27, and SCC-15. The relationship between the expression of lncRNA PCGEM1 and miR-148a and the clinicopathological information of patients was analyzed. The lncRNA PCGEM1-silenced cell line KB-siPCGEM1 and negative control (KB-NC) group were constructed, and KB was used as the blank control group. The effects of lncRNA PCGEM1 on the proliferation, invasion, and migration of KB cells were determined via MTT, Transwell, and scratch assays. The bioinformatics website starBase was used to predict the complementary binding microRNA (miRNA) of lncRNA PCGEM1. Furthermore, the genes that the miRNA could target and bind were predicted in accordance with the website www.microRNA.org. Western blotting analysis was used to detect the expression of TGF ß2/Smad2 signaling pathway proteins. RESULTS: qRT-PCR results showed that the expression level of lncRNA PCGEM1 and miR-148a in OSCC tissues was higher than that in normal tissues (P<0.05). The expression of lncRNA PCGEM1 and miR-148a in the cancer tissues of patients with different TNM grades, lymph node metastasis, and tissue differentiation was statistically significant (P<0.05). Compared with those in the blank control group and the KB-NC group, OD492 nm value was significantly decreased and cell mobility was significantly reduced in the KB-siPCGEM1 group (P<0.05). Bioinformatics predictions showed that lncRNA PCGEM1 could bind to miR-148a in a complementary manner and that miR-148a had a targeted binding site with TGF ß2. qRT-PCR and Western blotting analysis results showed that the expression levels of miR-148a, TGF ß2, and p-Smad2 in the KB-siPCGEM1 group were significantly lower than those in the blank control and KB-NC groups (P<0.05), and no statistically significant difference between the blank control group and the KB-NC group was observed (P>0.05). CONCLUSIONS: LncRNA PCGEM1 is highly expressed in OSCC. The high expression of lncRNA PCGEM1 may enhance the TGF ß2/Smad2 signaling pathway by upregulating miR-148a, thus promoting the development of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , RNA Longo não Codificante , Carcinoma de Células Escamosas/genética , Proliferação de Células , Células Epiteliais , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Transdução de Sinais , Proteína Smad2 , Fator de Crescimento Transformador beta2
11.
Nat Commun ; 11(1): 4755, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958772

RESUMO

We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincRNA fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an RNA-binding protein recently found to be implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally occurring genetic variations highly significant for sterol/steroid-related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance.


Assuntos
Homeostase , Oxigênio/metabolismo , RNA Longo não Codificante/fisiologia , Esteróis/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Colesterol/metabolismo , Estrogênios/metabolismo , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo , Humanos , Células MCF-7 , Fenótipo , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
12.
Hum Cell ; 33(4): 1081-1090, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32918701

RESUMO

Long non-coding RNAs (lncRNAs) function in rheumatoid arthritis (RA). The present work was designed to explore the roles of lncRNA PVT1 in RA and the related mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine mRNA level. The binding sites between PVT1 and miR-145-5p were verified by a dual-luciferase reporter assay. Furthermore, RA-FLSs were treated with TNF-α to establish the RA model. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed to detect cell proliferation. Flow cytometry and TUNEL assays were performed to detect cell apoptosis. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of inflammatory cytokines. PVT1 was significantly increased and miR-145-5p was decreased in synovial tissues of RA patients. miR-145-5p is a target miRNA of PVT1, and the levels of PVT1 and miR-145-5p in synovial tissues of RA patients were negatively correlated. In RA-FLSs, tumour necrosis factor-α (TNF-α) led to increased PVT1 levels and decreased miR-145-5p levels. Knockdown of PVT1 inhibited TNF-α-induced RA-FLS over-proliferation and reversed TNF-α-induced RA-FLS apoptosis reduction. Moreover, knockdown of PVT1 inhibited TNF-α-induced production of interleukin (IL)-1ß and IL-6 and the activation of NF-κB through miR-145-5p. PVT1 can regulate apoptosis and inflammatory responses in RA-FLSs by targeting miR-145-5p.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Proliferação de Células/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/fisiologia , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Adulto , Idoso , Apoptose/genética , Artrite Reumatoide/tratamento farmacológico , Células Cultivadas , Citocinas/metabolismo , Feminino , Expressão Gênica , Humanos , Inflamação/genética , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Necrose Tumoral alfa
13.
Hum Cell ; 33(4): 946-953, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32772230

RESUMO

Long noncoding RNA (lncRNA) is a newly identified type of noncoding RNA with a length of more than 200 nucleotides. The latest research shows that lncRNAs play important roles in the occurrence and development of human tumours by acting both as carcinogenic genes and as tumour suppressor genes. LncRNAs plays a role in various biological processes, such as cell growth, apoptosis, migration and invasion. The newly discovered lncRNA DDX11-AS1 is abnormally highly expressed in various malignant tumours, such as hepatocellular carcinoma, colorectal cancer, osteosarcoma, bladder cancer, NSCLC and gastric cancer. DDX11-AS1 mainly regulates the expression of related genes through direct or indirect ways to perform its functions in carcinogenicity. These results indicate that DDX11-AS1 may be a marker or therapeutic target of tumours. This review summarizes the biological function and mechanism of DDX11-AS1 in the process of tumour development.


Assuntos
RNA Helicases DEAD-box/genética , DNA Helicases/genética , Neoplasias/genética , Neoplasias/patologia , RNA Longo não Codificante/genética , Apoptose/genética , Biomarcadores Tumorais , Carcinogênese/genética , Proliferação de Células/genética , RNA Helicases DEAD-box/fisiologia , DNA Helicases/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor , Humanos , Terapia de Alvo Molecular , Invasividade Neoplásica/genética , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Oncogenes , Prognóstico , RNA Longo não Codificante/fisiologia
14.
Hum Cell ; 33(4): 1142-1154, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32776307

RESUMO

Long noncoding RNAs (lncRNAs) are abnormally expressed in many malignant tumors and involved in regulating the malignant phenotypes of cancer cells. However, the role of LINC00665 in colorectal cancer (CRC) and its regulatory mechanism remain unclear. In this study, real-time polymerase chain reaction (RT-PCR) was used to detect the expressions of LINC00665, miR-9-5p and activating transcription factor 1 (ATF1) mRNA in CRC tissues. The expression of ATF1 in CRC tissues was also detected by immunohistochemistry and Western blot. CCK-8 and colony formation assays were employed to detect cell proliferation. Cell cycle and apoptosis were detected by flow cytometry analysis. Scratch healing assay and Transwell test were exploited to detect cell migration and invasion. The targeting relationships between LINC00665 and miR-9-5p, and miR-9-5p and ATF1 were validated by dual luciferase reporter assay. We found that LINC00665 was significantly overexpressed in CRC tissues, and it was also negatively correlated with the expression of miR-9-5p and positively associated with the expression of ATF1. Besides, LINC00665 promoted the proliferation, migration and invasion of CRC cells, and inhibited cell apoptosis by sponging miR-9-5p. ATF1 was proved to be the downstream target of miR-9-5p and was indirectly regulated by LINC00665. Collectively, it is concluded that LINC00665 contributes to the progression of CRC by regulating miR-9-5p/ATF1 axis.


Assuntos
Fator 1 Ativador da Transcrição/genética , Fator 1 Ativador da Transcrição/metabolismo , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Apoptose/genética , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/metabolismo , Progressão da Doença , Marcação de Genes , Humanos , Invasividade Neoplásica/genética , RNA Longo não Codificante/metabolismo
15.
Hum Cell ; 33(4): 1240-1251, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32749665

RESUMO

The aim of this study is to investigate the effect of lncRNA DUXAP8 on proliferation and apoptosis of ovarian cancer cells, and to explore its potential mechanism. DUXAP8 interfering and overexpressing cell lines were constructed and the cell proliferation and apoptosis were tested. Hematoxylin-eosin, TdT-mediated dUTP nick end labeling, and immunohistochemistry were used to detect the effect of DUXAP8 on the ability of tumor formation. Quantitative real-time polymerase chain reaction and western blot were used to detect the mRNA and protein expression of miR-590-5p and YAP1, respectively. Dual luciferase assay was used to determine the target relationship between DUXAP8, miR-590-5p, and YAP1. DUXAP8 interference and miR-590-5p down-regulated cell lines were further constructed. Compared with normal ovarian cells, the expression of DUXAP8 in ovarian cancer cells was significantly increased, while the expression of miR-590-5p was decreased (p < 0.05). After DUXAP8 interference, cell proliferation and colony formation were decreased, and apoptosis was increased. The results of in vivo experiment are consistent with the in vitro experiments. The expression of miR-590-5p was up-regulated and the expression of YAP1 was decreased after DUXAP8 interference. Moreover, miR590-5p inhibitor can attenuate the effect of DUXAP8 interference on ovarian cancer cells. Taken together, lncRNA DUXAP8 can regulate the proliferation and apoptosis of ovarian cancer cells, and its mechanism may be related to the regulation of YAP1 gene by targeting miR-590-5p.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Feminino , Humanos , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas
16.
Life Sci ; 260: 118299, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827542

RESUMO

AIMS: The most typical pathological manifestation of retinopathy of prematurity (ROP) is Retinal neovascularization (RNV). Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to mediate angiogenesis. Our experiment aimed to research the effect and mechanism of the MALAT1 on RNV in ROP. MAIN METHODS: C57 mice was used to establish oxygen-introduced retinopathy (OIR), and divided into control, hyperoxia, hyperoxia control siRNA, and hyperoxia MALAT1 siRNA groups. KEY FINDINGS: It was shown that MALAT1 mRNA was high expressed in the retinas of OIR mice. Further studies revealed that after intravitreal injection of MALAT1 siRNA, the degree of retinopathy was significantly reduced compared with OIR group. In addition, the protein and mRNA expression levels of CCN1, AKT and VEGF were significantly decreased. This was accompanied by a decrease in inflammatory genes including IL-1ß, IL-6, and TNF-α compared with the hyperoxia control siRNA mice. SIGNIFICANCE: The result suggested that MALAT1 may be involved in the process of RNV in ROP and MALAT1 siRNA may be a promising agent for the treatment of ROP by inhibiting RNV.


Assuntos
RNA Longo não Codificante/fisiologia , Neovascularização Retiniana/fisiopatologia , Retinopatia da Prematuridade/fisiopatologia , Animais , Animais Recém-Nascidos , Proteína Rica em Cisteína 61/análise , Proteína Rica em Cisteína 61/genética , Modelos Animais de Doenças , Feminino , Hiperóxia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/farmacologia , RNA Mensageiro/análise , RNA Interferente Pequeno/administração & dosagem , Retina/química , Retinopatia da Prematuridade/etiologia , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/genética , Corpo Vítreo/efeitos dos fármacos
17.
Life Sci ; 260: 118305, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827544

RESUMO

AIM: The study aims to investigate the roles of LncRNA and miRNA in ferroptosis in brain ischemia/reperfusion (I/R) in vivo and in vitro. MATERIALS AND METHODS: qPCR assay was used to analyze lncRNA PVT1 and miR-214 expressions in acute ischemic stroke (AIS) patients. Then, we established brain I/R mice models and OGD/R PC12 cell models to analyze the mechanism of ferroptosis. I/R mice were treated by lncRNA PVT silencing or miR-214 overexpressing lentivirus via lateral ventricles. Infarct size was analyzed by TTC staining, accompanied by the detection of ferroptosis indicators through Perls'Prussian blue staining, iron kit, MDA kit, glutathione kit, GPx activities kit and Western blotting (WB). Dual luciferase reporter assay was used to assess whether miR-214 bound to PVT1, TP53 or TFR1. Co-IP analyzed the interplay of p53 with SLC7A11. KEY FINDINGS: We found that the levels of PVT1 were upregulated and miR-214 levels were downregulated in plasma of AIS patients. NIHSS score was positively correlated with PVT1 levels but was negatively with miR-214 levels. PVT1 silencing or miR-214 overexpression significantly reduced infarct size and suppressed ferroptosis in vivo. miR-214 overexpression markedly decreased PVT1 levels. Specifically, miR-214 could bind to 3'untranslated region (3'UTR) of PVT1, TP53 or TFR1. PVT1 overexpression or miR-214 silencing markedly abolished the effects of Ferrostatin-1 on ferroptosis indicators except for TFR1 expression. Besides, miR-214 silencing counteracted the effects of PVT1 knockdown on the ferroptosis-related proteins. CONCLUSION: PVT1 regulated ferroptosis through miR-214-mediated TFR1 and TP53 expression. There was a positive feedback loop of lncRNA PVT1/miR-214/p53 possibly.


Assuntos
Antígenos CD/fisiologia , Ferroptose/fisiologia , MicroRNAs/fisiologia , RNA Longo não Codificante/fisiologia , Receptores da Transferrina/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Animais , Isquemia Encefálica/fisiopatologia , Cicloexilaminas/farmacologia , Modelos Animais de Doenças , Feminino , Ferroptose/efeitos dos fármacos , Inativação Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Células PC12 , Fenilenodiaminas/farmacologia , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Ratos , Traumatismo por Reperfusão , Acidente Vascular Cerebral/fisiopatologia
18.
Hum Cell ; 33(4): 1281-1293, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32860589

RESUMO

The study aims to investigate how DANCR can alter the growth and metastasis of oral squamous cell carcinoma (OSCC) cells by regulating miR-216a-5p. The expression of DANCR and miR-216a-5p in OSCC patients and cells were measured. SCC15 and CAL-27 cells were selected to divide into Control, sh-NC, DANCR shRNA, DANCR, miR-216a-5p mimic, and DANCR + miR-216a-5p mimic groups. Dual-luciferase reporter gene assay was performed for the verification of the targeting relationship between miR-216a-5p and DANCR/Bcl-2/KLF12. We also quantified the abilities of OSCC cells regarding proliferation, invasion, migration and apoptosis, and the expression levels of apoptosis-related proteins were measured. Finally, the tumor-bearing nude mice were established to verify the effect of DANCR in vivo. Up-regulated DANCR expression and down-regulated miR-216a-5p expression were observed in both OSCC tissues and cells, and they were proven strongly correlated to the histological grade, clinical staging and lymph node metastasis of OSCC patients. Dual-luciferase reporter gene assay showed a target relationship between DANCR and miR-216a-5p, as well as between miR-216a-5p and Bcl-2/KLF12. Both DANCR shRNA and miR-216a-5p mimic decreased proliferative, migration and invasive abilities of OSCC cells with increased cell apoptosis. However, DANCR group showed completely opposite trends. Moreover, miR-216a-5p mimic could reverse the role of DANCR in promoting tumor growth. In-vivo experiment confirmed the inhibitory role of DANCR shRNA in tumor growth and metastasis. We concluded that DANCR may promote the growth and metastasis of OSCC cells and suppress OSCC cell apoptosis by sponging miR-216a-5p.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Metástase Linfática/genética , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/metabolismo
19.
Life Sci ; 257: 118013, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32603818

RESUMO

AIMS: Emerging literature illustrates critical roles of long noncoding RNAs (lncRNAs) in the progression of atherosclerosis. However, the biological functions and mechanism by which lncRNAs regulate the atherosclerosis remain unclear. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidative low-density lipoprotein (ox-LDL). RNA and protein levels were respectively measured using RT-qPCR and western blot. Molecular interaction was detected using luciferase reporter assay and chromatin immunoprecipitation (ChIP). Proliferation and migration were measured using CCK-8 and wound healing assay. KEY FINDINGS: Here, results unveiled that lncRNA SNHG7 was remarkedly up-regulated in ox-LDL exposed HUVECs. Gain and loss of function experiments showed that the SNHG7 repressed the proliferation and migration of HUVECs. Mechanistically, transcription factor E2F1 was found to target the promoter region of lncRNA SNHG7 and accelerated its expression. Moreover, miR-186-5p was found to bind with the 3'-UTR of SNHG7, meanwhile miR-186-5p also bound with the MMP2 mRNA 3'-UTR. SIGNIFICANCE: In conclusion, these results show the essential roles of E2F1/SNHG7/miR-186-5p/MMP2 axis on the proliferation and migration of endothelial cells, providing a potential therapeutic target for atherosclerosis.


Assuntos
Aterosclerose/metabolismo , Células Endoteliais/metabolismo , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Apoptose/genética , Aterosclerose/fisiopatologia , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Fator de Transcrição E2F1/metabolismo , Células Endoteliais/fisiologia , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipoproteínas LDL , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia
20.
Life Sci ; 257: 118114, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32693241

RESUMO

The world has witnessed a high morbidity and mortality caused by SARS-CoV-2, and global death toll is still rising. Exaggerated inflammatory responses are thought to be more responsible for infiltrated immune cells accumulation, organ damage especially lung, dyspnea, and respiratory failure rather than direct effect of viral replication. IL-6 and NLRP3 inflammasome are the major immune components in immune responses stimulation upon pathogen infection. It's noteworthy that the function and expression of these components are remarkably influenced by non-coding RNAs including long non-coding RNAs. Given the potential role of these components in organ damage and pathological manifestations of patients infected with COVID-19, their blockage might be a hopeful and promising treatment strategy. Notably, more study on long non-coding RNAs involved in inflammatory responses could elevate the efficacy of anti-inflammatory therapy. In this review we discuss the potential impact of IL-6 and NLRP3 inflammasome blocker drugs on inflammatory responses, viral clearance, and pathological and clinical manifestations. Collectively, anti-inflammatory strategy might pave the way to diminish clinical and pathological manifestations and thereby discharging patients infected with COVID-19 from hospital.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Interleucina-6/imunologia , Pneumonia Viral/imunologia , RNA Longo não Codificante/fisiologia , Anti-Inflamatórios/farmacologia , Betacoronavirus/imunologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/metabolismo , Citocinas/genética , Citocinas/imunologia , Humanos , Inflamassomos/imunologia , Inflamação/imunologia , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Pandemias , Pneumonia Viral/metabolismo , RNA Longo não Codificante/genética
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