Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 16.173
Filtrar
1.
J Hazard Mater ; 416: 125878, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492818

RESUMO

With the increased appreciation for the significance of noncoding RNAs (ncRNAs), the present research aimed to determine the role of competing endogenous RNA (ceRNA) in the process of particulate matter (PM) exposure-induced pulmonary damage. Alterations in messenger RNA (RNA), microRNA and long non-coding RNA (lncRNA) profiles of human bronchial epithelial (HBE) cells treated with PM were analyzed by microarray assays. Next, we identified that lncRNA taurine upregulated gene 1 (TUG1) acted as a competing endogenous RNA for microRNA-222-3p (miR-222-3p) and subsequently attenuated the inhibitory effect of miR-222-3p on CUGBP elav-like family member 1 (CELF1). The binding potency among ceRNAs was verified by RNA immunoprecipitation (RIP) assay and dual-luciferase reporter assay. Knockdown of TUG1 attenuated HBE cell apoptosis and cell cycle arrest by downregulation of CELF1 and protein 53 (p53). Further, we confirmed that Tug1/mir-222-3p/CELF1/p53 network aggravated PM-induced airway hyper-reactivity (AHR) in mice. In summary, our novel findings revealed that TUG1 triggered dysfunction of pulmonary cells followed by PM exposure by serving as a sponge for miR-222-3p and thereby upregulating the expression of CELF1and p53.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Proliferação de Células , Camundongos , MicroRNAs/genética , Material Particulado/toxicidade , RNA Longo não Codificante/genética , Taurina
2.
BMC Genomics ; 22(1): 638, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34479506

RESUMO

BACKGROUND: LncRNAs are extensively involved in plant biological processes. However, the lack of a comprehensive lncRNA landscape in moso bamboo has hindered the molecular study of lncRNAs. Moreover, the role of lncRNAs in secondary cell wall (SCW) biosynthesis of moso bamboo is elusive. RESULTS: For comprehensively identifying lncRNA throughout moso bamboo genome, we collected 231 RNA-Seq datasets, 1 Iso-Seq dataset, and 1 full-length cDNA dataset. We used a machine learning approach to improve the pipeline of lncRNA identification and functional annotation based on previous studies and identified 37,009 lncRNAs in moso bamboo. Then, we established a network of potential lncRNA-coding gene for SCW biosynthesis and identified SCW-related lncRNAs. We also proposed that a mechanism exists in bamboo to direct phenylpropanoid intermediates to lignin or flavonoids biosynthesis through the PAL/4CL/C4H genes. In addition, we identified 4 flavonoids and 1 lignin-preferred genes in the PAL/4CL/C4H gene families, which gained implications in molecular breeding. CONCLUSIONS: We provided a comprehensive landscape of lncRNAs in moso bamboo. Through analyses, we identified SCW-related lncRNAs and improved our understanding of lignin and flavonoids biosynthesis.


Assuntos
Parede Celular , Redes Reguladoras de Genes , Poaceae , RNA Longo não Codificante , Parede Celular/genética , Regulação da Expressão Gênica de Plantas , Poaceae/genética , RNA Longo não Codificante/genética , RNA de Plantas/genética
3.
BMC Plant Biol ; 21(1): 410, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493227

RESUMO

BACKGROUND: Water deficit is an abiotic stress that retards plant growth and destabilizes crop production. Long non coding RNAs (lncRNAs) are a class of non-coding endogenous RNAs that participate in diverse cellular processes and stress responses in plants. lncRNAs could function as competing endogenous RNAs (ceRNA) and represent a novel layer of gene regulation. However, the regulatory mechanism of lncRNAs as ceRNA in drought stress response is yet unclear. RESULTS: In this study, we performed transcriptome-wide identification of drought-responsive lncRNAs in rice. Thereafter, we constructed a lncRNA-mediated ceRNA network by analyzing competing relationships between mRNAs and lncRNAs based on ceRNA hypothesis. A drought responsive ceRNA network with 40 lncRNAs, 23 miRNAs and 103 mRNAs was obtained. Network analysis revealed TCONS_00021861/miR528-3p/YUCCA7 regulatory axis as a hub involved in drought response. The miRNA-target expression and interaction were validated by RT-qPCR and RLM-5'RACE. TCONS_00021861 showed significant positive correlation (r = 0.7102) with YUCCA7 and negative correlation with miR528-3p (r = -0.7483). Overexpression of TCONS_00021861 attenuated the repression of miR528-3p on YUCCA7, leading to increased IAA (Indole-3-acetic acid) content and auxin overproduction phenotypes. CONCLUSIONS: TCONS_00021861 could regulate YUCCA7 by sponging miR528-3p, which in turn activates IAA biosynthetic pathway and confer resistance to drought stress. Our findings provide a new perspective of the regulatory roles of lncRNAs as ceRNAs in drought resistance of rice.


Assuntos
Oryza/genética , RNA Longo não Codificante/genética , Desidratação/genética , Secas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Células do Mesofilo/ultraestrutura , MicroRNAs/genética , Folhas de Planta/genética , RNA Mensageiro/genética , RNA de Plantas , Espécies Reativas de Oxigênio/metabolismo
4.
Medicine (Baltimore) ; 100(36): e27178, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516515

RESUMO

ABSTRACT: Small nucleolar RNA host gene 16 (SNHG16) has recently been reported as a potential biomarker in various cancers. However, the prognostic value of SNHG16 in hepatocellular carcinoma (HCC) has not been investigated yet. Therefore, the purpose of this study was to reveal the association between SNHG16 expression and clinicopathological characteristics of HCC.Standards-compliant literature was retrieved from multiple public databases, and data on overall survival, disease-free survival, and clinicopathological characteristics related to SNGH16 were extracted and meta-analysis was performed. Additionally, the Cancer Genome Atlas data were analyzed through the gene expression profiling interactive analysis database to verify previous results.A total of 5 reports involving 410 patients with HCC were enrolled. The high expression of SNHG16 indicated worse overall survival (hazard ratio, 2.10; 95% CI, 1.22-3.60; P = .007) and disease-free survival (hazard ratio, 3.38; 95% CI, 1.10-10.40; P = .03). Additionally, the high expression of SNHG16 predicted a larger tumor size, metastasis, and advanced TNM stage.SNHG16 could serve as a potential biomarker of poor prognosis in HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Prognóstico
5.
Planta ; 254(4): 72, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519918

RESUMO

MAIN CONCLUSION: We have predicted miRNAs, their targets and lncRNAs from the genome of Brassica oleracea along with their functional annotation. Selected miRNAs and their targets are experimentally validated. Roles of these non-coding RNAs in post-transcriptional gene regulation are also deciphered. Cauliflower (Brassica oleracea var. Botrytis) is an important vegetable crop for its dietary and medicinal values with rich source of vitamins, dietary fibers, flavonoids and antioxidants. MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs), which regulate gene expression by inhibiting translation or by degrading messenger RNAs (mRNAs). On the other hand, long non-coding RNAs (lncRNAs) are responsible for the up regulation and the down regulation of transcription. Although the genome of cauliflower is reported, yet the roles of these ncRNAs in post-transcriptional gene regulation (PTGR) remain elusive. In this study, we have computationally predicted 355 miRNAs, of which 280 miRNAs are novel compared to miRBase 22.1. All the predicted miRNAs belong to 121 different families. We have also identified 934 targets of 125 miRNAs along with their functional annotation. These targets are further classified into biological processes, molecular functions and cellular components. Moreover, we have predicted 634 lncRNAs, of which 61 are targeted by 30 novel miRNAs. Randomly chosen 10 miRNAs and 10 lncRNAs are experimentally validated. Five miRNA targets including squamosa promoter-binding-like protein 9, homeobox-leucine zipper protein HDG12-like, NAC domain-containing protein 100, CUP-SHAPED COTYLEDON 1 and kinesin-like protein NACK2 of four miRNAs including bol-miR156a, bol-miR162a, bol-miR164d and bol-miR2673 are also experimentally validated. We have built network models of interactions between miRNAs and their target mRNAs, as well as between miRNAs and lncRNAs. Our findings enhance the knowledge of non-coding genome of cauliflower and their roles in PTGR, and might play important roles in improving agronomic traits of this economically important crop.


Assuntos
Brassica , MicroRNAs , RNA Longo não Codificante , Brassica/genética , Regulação da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro
6.
Nat Commun ; 12(1): 5232, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475402

RESUMO

Disseminated tumor cells often fall into a long term of dormant stage, characterized by decreased proliferation but sustained survival, in distant organs before awakening for metastatic growth. However, the regulatory mechanism of metastatic dormancy and awakening is largely unknown. Here, we show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels of dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) NR2F1-AS1 (NAS1) is up-regulated in the dormant mesenchymal-like BCSCs, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanistically, NAS1 binds to NR2F1 mRNA and recruits the RNA-binding protein PTBP1 to promote internal ribosome entry site (IRES)-mediated NR2F1 translation, thus leading to suppression of ΔNp63 transcription by NR2F1. Furthermore, ΔNp63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs. Overall, the study links BCSC plasticity with metastatic dormancy, and reveals the lncRNA as an important regulator of both processes.


Assuntos
Neoplasias da Mama/patologia , Fator I de Transcrição COUP/genética , Neoplasias Pulmonares/secundário , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Regiões 5' não Traduzidas , Animais , Neoplasias da Mama/genética , Fator I de Transcrição COUP/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Humanos , Sítios Internos de Entrada Ribossomal , Pulmão/patologia , Neoplasias Pulmonares/genética , Camundongos , Invasividade Neoplásica , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
7.
BMC Genomics ; 22(1): 653, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34511071

RESUMO

BACKGROUND: As non-coding RNA molecules of more than 200 bp in length, long non-coding RNAs (lncRNAs) play a variety of roles in biological processes, including regulating the immune responses to bacterial infections. In recent years, there have been many in-depth studies on mammalian lncRNAs, but the relevant studies in fish are very limited. Meanwhile, since lncRNAs are not conserved among species, it is difficult to apply the existing results directly to unstudied species. RESULTS: To obtain the information of lncRNAs in Megalobrama amblycephala, one of the most economically important freshwater fish in China, also to better understand the biological significance of lncRNAs in the immunity system, the fish liver at 0, 4, 12, 24, and 72 h post Aeromonas hydrophila infection (hpi) were obtained for lncRNA-sequencing (lncRNA-seq). A total of 14,849 lncRNAs were identified, and 2196 lncRNAs showed significant differences at different time points post A. hydrophila infection. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the target genes of the differentially expressed lncRNAs were enriched in several pathways related to immune such as apoptosis, inflammation, and immune response. Time-specific modules were then identified, using weighted correlation network analysis (WGCNA), and 28 modules significantly correlated with different time point after infection were found. Furthermore, four immune-related genes and six lncRNAs in the time-specific modules were subsequently verified by RT-qPCR. CONCLUSIONS: The above findings reveal the discovery of widespread differentially expressed lncRNAs in the M. amblycephala liver post A. hydrophila infection, suggesting that lncRNAs might participate in the regulation of host response to bacterial infection, enriching the information of lncRNAs in teleost and providing a resources basis for further studies on the immune function of lncRNAs.


Assuntos
Cyprinidae , RNA Longo não Codificante , Aeromonas hydrophila , Animais , Cyprinidae/genética , Fígado , RNA Longo não Codificante/genética , RNA Mensageiro/genética
8.
J Int Med Res ; 49(9): 3000605211039798, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34521242

RESUMO

OBJECTIVE: The long non-coding RNA (lncRNA) growth arrest­specific transcript 5 (GAS5) plays an important role in various tumors, and an increasing number of studies have explored the association of the GAS5 rs145204276 polymorphism with cancer risk with inconclusive results. METHODS: PubMed, Medline, EMBASE, Cochrane databases, and Web of Science were searched, and nine studies involving 6107 cases and 7909 controls were deemed eligible. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the relationship between rs145204276 and cancer risk in six genetic models. RESULTS: The pooled results suggest that the variant allele del was not associated with overall cancer risk. However, the subgroup analysis showed that allele del was significantly associated with a 22% decreased risk of gastrointestinal cancer (OR = 0.78, 95% CI: 0.72-0.85). Both sensitivity analyses and trial sequential analyses (TSA) demonstrated that the subgroup results were reliable and robust. Moreover, False-Positive Report Probability (FPRP) analysis indicated that the results had true significant correlations. CONCLUSION: These findings provide evidence that the GAS5 rs145204276 polymorphism is associated with the susceptibility to gastrointestinal cancer. Further studies with different ethnicities and larger sample sizes are warranted to confirm these results.


Assuntos
Neoplasias , RNA Longo não Codificante , Predisposição Genética para Doença , Humanos , Neoplasias/genética , Polimorfismo Genético , RNA Longo não Codificante/genética , Risco
9.
Ann Palliat Med ; 10(8): 9206-9214, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488406

RESUMO

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis. The hyperproliferation and hyperkeratosis of keratinocytes is a key step in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) and mRNAs regulate gene expression in various biological process, including the function of keratinocytes. This research investigated the expression profile of lncRNAs and mRNAs in keratinocytes of patients with psoriasis vulgaris. METHODS: The expression of lncRNAs and mRNAs in keratinocytes from patients with psoriasis vulgaris and healthy patients was examined and compared using microarrays. Quantitative polymerase chain reaction (qPCR) and bioinformatic analysis was also performed. DAVID and KEGG were used to analyze the gene function. The competing endogenous RNA (ceRNA) network was also constructed. RESULTS: A total of 48 lncRNAs and 17 mRNAs were differentially expressed in keratinocytes of psoriasis vulgaris. Quantitative PCR data showed that the expression of lnc-AGXT2L1-2:2 (P=0.009) and NR_027032 (P=0.033) was up-regulated in psoriasis vulgaris. The lncRNA-miRNA-mRNA interaction network was established. The mRNA showing the most connections with the lncRNAs and miRNAs was CEP104. The miRNA showing the most connections with the lncRNAs and mRNAs was miR-484. The lncRNA showing the most connections with miRNAs and mRNAs was ENST00000494887. CONCLUSIONS: The identification of the differentially expressed lncRNAs and mRNAs in psoriasis vulgaris provides significant insights into the pathogenesis of the disease.


Assuntos
Psoríase , RNA Longo não Codificante , Redes Reguladoras de Genes/genética , Humanos , Queratinócitos , Psoríase/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
10.
J Int Med Res ; 49(9): 300060520973137, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34528496

RESUMO

OBJECTIVE: The objective was to explore the expression and potential functions of long noncoding RNA (lncRNA) and mRNAs in human breast cancer (BC). METHODS: Differentially expressed lncRNAs and mRNAs were identified and annotated in BC tissues by using the Agilent human lncRNA assay (Agilent Technologies, Santa Clara, CA, USA) and RNA sequencing. After identification of lncRNAs and mRNAs through quantitative reverse transcription polymerase chain reaction, we conducted a series of functional experiments to confirm the effects of knockdown of one lncRNA, TCONS_00029809, on the progression of BC. RESULTS: We discovered 238 lncRNAs and 200 mRNAs that were differentially expressed in BC tissues and para-carcinoma tissue. We showed that differentially expressed mRNAs were related to biological adhesion and biological regulation and mainly enriched in cytokine-cytokine receptor interaction, metabolic pathways, and PI3K-Akt signaling pathway. We created a protein-protein interaction network to analyze the proteins enriched in these pathways. We demonstrated that silencing of TCONS_00029809 remarkably inhibited proliferation, invasion, and migration of BC cells, and accelerated their apoptosis. CONCLUSIONS: We identified a large number of differentially expressed lncRNAs and mRNAs, which provide data useful in understanding BC carcinogenesis. The lncRNA TCONS_00029809 may be involved in the development of BC.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Apoptose , Neoplasias da Mama/genética , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Fosfatidilinositol 3-Quinases , RNA Longo não Codificante/genética , RNA Mensageiro/genética
11.
World J Surg Oncol ; 19(1): 281, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535152

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are related to colorectal cancer (CRC) development. However, the role and mechanism of lncRNA LINC01224 in CRC development are largely unknown. METHODS: LINC01224, Yin Yang 1 (YY1), microRNA (miR)-485-5p, and myosins of class VI (MYO6) levels were examined using quantitative reverse transcription polymerase chain reaction and western blotting. Functional analyses were processed through CCK-8, colony formation, flow cytometry, transwell, and xenograft analyses. Dual-luciferase reporter, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation, and pull-down assays were conducted to analyze the binding interaction. RESULTS: LINC01224 abundance was elevated in CRC tissue samples and cell lines. Elevated LINC01224 might indicate the lower 5-year overall survival in 52 CRC patients. LINC01224 was upregulated via the transcription factor YY1. LINC01224 knockdown restrained CRC cell proliferation, migration, and invasion and increased apoptosis. MiR-485-5p was sponged by LINC01224, and miR-485-5p downregulation relieved the influence of LINC01224 interference on CRC progression. MYO6 was targeted via miR-485-5p and regulated via LINC01224/miR-485-5p axis. MiR-485-5p overexpression suppressed CRC cell proliferation, migration, and invasion and facilitated apoptosis. MYO6 upregulation mitigated the role of miR-485-5p. LINC01224 knockdown decreased xenograft tumor growth. CONCLUSION: YY1-induced LINC01224 regulates CRC development via modulating miR-485-5p/MYO6 axis.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Proliferação de Células , Neoplasias Colorretais/genética , Humanos , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética
12.
J Pharm Biomed Anal ; 204: 114285, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34333453

RESUMO

Lateral flow assay (LFA) is a flexible, simple, low-costpoint-of-care platform for rapid detection of disease-specific biomarkers. Importantly, the ability of the assay to capture the circulating bio-molecules has gained significant attention, as it offers a potential minimal invasive system for early disease diagnosis and prognosis. In the present article, we review an innovative concept of LFA-based detection of circulating long non-coding RNAs (lncRNAs), one of the key regulators of fundamental biological processes. In addition, their disease-specific expression pattern and presence in biological fluids at differential levels make them excellent biomarker candidates for cancer detection. Our article also provides an update on the requirements for developing and improving such systems and discusses the key aspects of material selection, operational concepts, principles and conceptual design. We assume that the reviewed points will be helpful to improve the diagnostic applicability of LFA based lncRNA detection in cancer diagnosis.


Assuntos
Neoplasias , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Sistemas Automatizados de Assistência Junto ao Leito , Prognóstico , RNA Longo não Codificante/genética
13.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445087

RESUMO

The miR-31 host gene (MIR31HG) encodes a long non-coding RNA (LncRNA) that harbors miR-31 in its intron 2; miR-31 promotes malignant neoplastic progression. Overexpression of MIR31HG and of miR-31 occurs during oral squamous cell carcinoma (OSCC). However, the downstream effectors modulated by MIR31HG during OSCC pathogenesis remain unclear. The present study identifies up-regulation of MIR31HG expression during the potentially premalignant disorder stage of oral carcinogenesis. The potential of MIR31HG to enhance oncogenicity and to activate Wnt and FAK was identified when there was exogenous MIR31HG expression in OSCC cells. Furthermore, OSCC cell subclones with MIR31HG deleted were established using a Crispr/Cas9 strategy. RNA sequencing data obtained from cells expressing MIR31HG, cells with MIR31HG deleted and cells with miR-31 deleted identified 17 candidate genes that seem to be modulated by MIR31HG in OSCC cells. A TCGA database algorithm pinpointed MMP1, BMP2 and Limb-Bud and Heart development (LBH) as effector genes controlled by MIR31HG during OSCC. Exogenous LBH expression decreases tumor cell invasiveness, while knockdown of LBH reverses the oncogenic suppression present in MIR31HG deletion subclones. The study provides novel insights demonstrating the contribution of the MIR31HG-LBH cascade to oral carcinogenesis.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Humanos , Neoplasias Bucais/patologia , Regulação para Cima
14.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445100

RESUMO

Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways.


Assuntos
Endometriose/genética , Endométrio/patologia , Células Epiteliais/patologia , RNA Longo não Codificante/genética , Adulto , Linhagem Celular , Proliferação de Células , Endometriose/patologia , Endométrio/citologia , Endométrio/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Regulação para Cima , Adulto Jovem
15.
J Biomed Nanotechnol ; 17(7): 1380-1391, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446141

RESUMO

Esophageal cancer is one of the most common human malignancies and ranks sixth for global mortality; the major histological type is esophageal squamous cell carcinoma (ESCC). Here we assessed the effect of long non-coding (lnc) RNA OIP5-AS1 on the miR-30a-5p/Forkhead box protein D1 (FOXD1) axis in ESCC and investigated the underlying mechanism involving the ERK1/2 signaling pathway. lnc RNA OIP5-AS1 was highly expressed in human ESCC tissues and cells, targeted miR-30a-5p, and inhibited miR-30a-5p expression. Additionally, in human ESCC tissues, miR-30a-5p was poorly expressed, whereas FOXD1 mRNA and protein were highly expressed, with a negative correlation between miR-30a-5p and FOXD1 expression. miR-30a-5p targeted and inhibited FOXD1 expression. FOXD1 promoted the proliferation and invasion of ESCC and was related to the ERK1/2 signaling pathway; ERK1/2 inhibitors (LY-3214996) reversed the biological function of FOXD1. miR-30a-5p combined with FOXD1 regulated ERK1/2 expression and inhibited tumor growth in vivo. In this study, micro- and nano-particles were used as carriers to construct Nanocapsules carrying miR-30a-5p mimics and miR-30a-5p inhibitor through self-assembly method, so as to realize an efficient Nanocapsules delivery system of miR-30a-5p to esophageal cancer cells. It provides insights into targeted drug therapy and the development of micro- and nano-particles carriers.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Transfecção
16.
BMC Genomics ; 22(1): 593, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348644

RESUMO

BACKGROUND: The mutation of insulin-like growth factor 2 (IGF2 mutation) that a single-nucleotide substitution (G→A) in the third intron of IGF2 abrogates the interaction with zinc finger BED-type containing 6 (ZBED6) and leads to increased muscle mass in pigs. IGF2 mutation knock-in (IGF2 KI) and ZBED6 knockout (ZBED6 KO) lead to changes in IGF2 expression and increase muscle mass in mice and pigs. Long noncoding RNAs (lncRNAs) may participate in numerous biological processes, including skeletal muscle development. However, the role of the ZBED6-lncRNA axis in skeletal muscle development is poorly characterized. RESULTS: In this study, we assembled transcriptomes using RNA-seq data published in previous studies by our group and identified 11,408 known lncRNAs and 2269 potential lncRNAs in seven tissues, heart, longissimus dorsi, gastrocnemius muscle, liver, spleen, lung and kidney, of ZBED6 KO (lean mass model) and WT Bama pigs. ZBED6 affected the expression of 1570 lncRNAs (differentially expressed lncRNAs [DE-lncRNAs]; log2-fold change ≥ 1, nominal p-value ≤ 0.05) in the seven examined tissues. The expressed lncRNAs (FPKM > 0.1) exhibited tissue-specific patterns in WT pigs. Specifically, 3410 lncRNAs were expressed exclusively in only one tissue. Potential functions of lncRNAs were indirectly predicted by searching their target cis- and trans-regulated protein-coding genes. LncRNAs with tissue-specific expression influence numerous genes related to tissue functions. Weighted gene coexpression network analysis (WGCNA) of 1570 DE-lncRNAs between WT and ZBED6 KO pigs was used to define the following six lncRNA modules specific to different tissues: skeletal muscle, heart, lung, spleen, kidney and liver modules. Furthermore, by conjoint analysis of longissimus dorsi data (tissue-specific expression, muscle module and DE-lncRNAs) and ChIP-PCR revealed NONSUSG002145.1 (adjusted p-values = 0.044), which is coexpressed with the IGF2 gene and binding with ZBED6, may play important roles in ZBED6 KO pig skeletal muscle development. CONCLUSIONS: These findings indicate that the identified lncRNAs may play essential roles in tissue function and regulate the mechanism of ZBED6 action in skeletal muscle development in pigs. To our knowledge, this is the first study describing lncRNAs in ZBED6 KO pigs. These results may open new research directions leading to a better understanding of the global functions of ZBED6 and of lncRNA functions in skeletal muscle development in pigs.


Assuntos
RNA Longo não Codificante , Animais , Íntrons , Camundongos , Desenvolvimento Muscular , Músculo Esquelético/metabolismo , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Suínos/genética , Transcriptoma
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1123-1128, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362491

RESUMO

OBJECTIVE: To observe the effects of down-regulation of long non-coding RNA HOX antisense intergenic RNA myeloid 1 (LncRNA-HOTAIRM1) to the proliferation and apoptosis of Jurkat in human leukemia T lymphocytes, and explore its mechanism. METHODS: Jurkat cells were cultured in vitro and randomly divided into control group, HOTAIRM1 siRNA-NC group and HOTAIRM1 siRNA group; the expressions of LncRNA-HOTAIRM1 mRNA, KIT receptor tyrosine kinase (KIT) mRNA and serine threonine kinase (AKT) mRNA in Jurkat cells were detected by real-time fluorescence quantification (RT-qPCR); the proliferation of Jurkat cells in each groups was detected by CCK-8 method; the apoptosis of Jurkat cells in each groups was detected by Annexin V-FITC/PI double staining; the expressions of KIT, AKT, p-KIT, p-AKT, B-lymphoma-2 gene (BCL-2) and Caspase-3 were detected by Western blot. RESULTS: Compared with the cells in the control group and HOTAIRM1 siRNA-NC group, the expression level of LncRNA-HOTAIRM1 mRNA, cell survival rate, expression levels of KIT mRNA, AKT mRNA, p-KIT, p-AKT and BCL-2 proteins in Jurkat cells in HOTAIRM1 siRNA group were significantly lower (P<0.05), while the expression level of Cleared Caspase-3 protein and Jurkat cell apoptosis rate were significantly higher (P<0.05). CONCLUSION: LncRNA-HOTAIRM1 may inhibit Jurkat cell proliferation and induce apoptosis through KIT/AKT signaling pathway.


Assuntos
RNA Longo não Codificante , Apoptose , Proliferação de Células , Regulação para Baixo , Humanos , Células Jurkat , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 812-817, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365633

RESUMO

OBJECTIVE: To study the effect of silencing LncRNA SNHG7 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its targeted regulation on miR-181b-5p. METHODS: Rat cardiomyocytes H9c2 were cultured in vitro and randomly divided into control group, H/R group, H/R + si-NC group, H/R + si-SNHG7 group, H/R + si-SNHG7 + anti-miR-NC group and H/R + si-SNHG7 + anti-miR-181b-5p group. The content of lactate dehydrogenase (LDH), malondialedhyde (MDA) and the activity of superoxide dismutase (SOD) were detected. Flow cytometry was carried out to detect the rate of apoptosis. qRT-PCR was used to detect the expression of SNHG7 and miR-181b-5p. Dual luciferase report experiment was used to verify the targeting relationship between SNHG7 and miR-181b-5p. Western blotting was used to detect the expression of Bax and Bcl-2. RESULTS: Compared with the control group, the H/R group showed significantly increased SNHG7 expression in cardiomyocytes, reduced miR-181b-5p expression, higher levels of LDH and MDA, reduced activity of SOD, increased cell apoptosis rate, higher level of Bax protein, and reduced level of Bcl-2 protein (all P< 0.05). Compared with the H/R and H/R + si-NC groups, the H/R + si-SNHG7 group had significantly reduced level of LDH and MDA, increased activity of SOD, reduced apoptosis rate, reduced level of Bax protein, increased level of Bcl-2 protein (all P< 0.05). The dual luciferase report experiment confirmed that SNHG7 could target miR-181b-5p. Interference with the expression of miR-181b-5p could reduce the effect of silencing SNHG7 on H/R-induced cardiomyocyte oxidative stress and apoptosis. CONCLUSION: Silencing SNHG7 may inhibit H/R-induced cardiomyocyte oxidative stress and apoptosis by up-regulating the expression of miR-181b-5p, thereby exerting a protective effect on cardiomyocytes.


Assuntos
MicroRNAs , Traumatismo por Reperfusão Miocárdica , RNA Longo não Codificante , Animais , Apoptose , Hipóxia , MicroRNAs/genética , Miócitos Cardíacos , RNA Longo não Codificante/genética , Ratos
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 343-348, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374251

RESUMO

Objective: To analyze the long non-coding RNA (lncRNA) and messenger RNA (mRNA) co-expression network changes induced by mtDNA3010A/G mutation in acute hypoxia, and to investigate the role of key lncRNA and mRNA in the regulation of gene expression induced by hypoxia. Methods: The genotype combinations A-C-C and G-C-C of mitochondrial DNA 3010-5178-10400 were screened, and genotypes of mtDNA3010A and mtDNA3010G fusion cells were constructed by using osteosarcoma cell treated by ethidium bromide without mitochondrion (ρ0206 cell) as donors. After treatment with 1% O2 24 h, the lncRNA - mRNA expression chip was applied to detect the differently expressed lncRNA and mRNA in two kinds of fusing cells, and fluorescence quantitative polymerase chain method was used to verify differently expressed mRNA. Bioinformatics methods were applied to build co-expression network of lncRNA-mRNA, predict target genes of differently expressed lncRNA, and the functions of differently expressed mRNA and target genes predicted by lncRNA were also analyzed based on gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) forecast analysis. Results: After treatment with 1% O2 for 24 h, compared with mtDNA3010G fusion cells: 688 lncRNAs were up-regulated, 21 were more than 2 times; 1098 were down-regulated, and 4 were more than 2 times. There were 1151 mRNA expressions up-regulated, 14 were more than 2 times, 539 mRNA expressions were down-regulated, and 3 were more than 2 times. Conclusion: MtDNA3010A/G genotype mutation under hypoxia is able to affect the lncRNA-mRNA regulatory network, and the differentially expressed lncRNA and mRNA may play an important role in regulation network of gene expression induced by hypoxia, which is expected to be a target for the regulation of hypoxia reaction from the perspective of mitochondria.


Assuntos
RNA Longo não Codificante , Perfilação da Expressão Gênica , Genótipo , Humanos , Hipóxia/genética , Mutação , RNA Longo não Codificante/genética , RNA Mensageiro/genética
20.
Science ; 373(6555): 662-673, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34353949

RESUMO

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. Here, we demonstrate that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine (Phe), musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that exhibit liver enrichment. Treatment with GalNAc-HULC mimics reduced excessive Phe in Pair -/- and Pah R408W/R408W mice and improved the Phe tolerance of these mice.


Assuntos
Fenilalanina Hidroxilase/metabolismo , Fenilalanina/metabolismo , Fenilcetonúrias/genética , RNA Longo não Codificante/genética , Acetilgalactosamina , Animais , Biopterina/análogos & derivados , Biopterina/metabolismo , Biopterina/uso terapêutico , Dieta , Modelos Animais de Doenças , Feminino , Hepatócitos/metabolismo , Humanos , Fígado/embriologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Conformação de Ácido Nucleico , Fenilalanina/administração & dosagem , Fenilalanina Hidroxilase/deficiência , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/tratamento farmacológico , Fenilcetonúrias/metabolismo , Ligação Proteica , RNA Longo não Codificante/química , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...