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Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.
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Objective To detect the expression of DCST1-AS1 in non-small cell lung cancer and explore its effect on malignant biological behavior of cancer cells.Methods The tissues and corresponding adjacent tissues from 65 patients with non-small cell lung cancer were collected,and the normal human bronchial epithelial cells 16HBE and the non-small cell lung cancer cell lines(A549,H1299,H1650 and HCC827)were cultured in vitro.The expression levels of DCST1-AS1 and miR-29b in tissues and cells were detected by RT-qPCR assay,and the correlation between the DCST1-AS1 expression and the clinical characteristics of patients with non-small cell lung cancer were analyzed.A549 cells were divided into the control group,the si-NC group,the si-DCST1-AS1 group,the si-DCST1-AS1+ anti-NC group and the si-DCST1-AS1+anti-miR-29b group.The cell proliferation was detected by CCK-8 assay and clone formation assay,the invasion and migration of cells were detected by Transwell;the expression of E-cadherin,Vimentin and N-cadherin was detected by Western blot.Results The expression of DCST1-AS1 increased and the expression of miR-29b decreased in non-small cell lung cancer tissues and cells(P<0.05).The expression of DCST1-AS1 was correlated with TNM stage,differentiated degree of tissue,lymph node metastasis and pathological types in non-small cell lung cancer patients(P<0.05).Compared with the control group or the si-NC group,the expression of DCST1-AS1,OD value,number of colony-forming cells,migration cells and invasion cells and the expression of Vimentin and N-cadherin in A549 cells of the si-DCST1-AS1 group decreased(P<0.05),while the expression of miR-29b and E-cadherin increased(P<0.05).Knocking down miR-29b could significantly reduce the effect of down-regulation of DCST1-AS1 expression on the malignant biological behavior of A549 cells.Conclusion DCST1-AS1 is highly expressed in non-small cell lung cancer,knocking down DCST1-AS1 may inhibit the malignant biological behavior of non-small cell lung cancer cells by up-regulating the expression of miR-29b.
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Long non-coding RNAs (lncRNAs) are related to the initiation and progression of tumor and regulate various cellular processes including growth, invasion, migration, and apoptosis. Understanding the roles and mechanisms of lncRNAs in regulating cancer progression is crucial for formulating novel therapeutic strategies. Although lncRNA DCST1-antisense RNA 1(AS1) has been implicated in several cancers, its role in the progression of colorectal cancer (CRC) remains to be explored. This study focuses on elucidating the function of lncRNA DCST1-AS1 in CRC development and its underlying mechanism. We found that the expression of lncRNA DCST1-AS1 was up-regulated in CRC tissues and cell lines, and CRC patients with high lncRNA DCST1-AS1 expression were associated with a poor prognosis. Loss-of-function and gain-of-function experiment in CRC cell lines confirmed that lncRNA DCST1-AS1 promoted the malignant phenotype of CRC cells, including cell proliferation, colony formation, migration, and invasion. In addition, we identified the binding sites between lncRNA DCST1-AS1 and hsa-miR-582-5p, and between hsa-miR-582-5p and High Mobility Group Box 1 (HMGB1) through DIANA Tools and TargetScan database, which was further confirmed by dual-luciferase reporter assay. Functional assay further confirmed the crucial role of lncRNA DCST1-AS1/hsa-miR-582-5p/HMGB1 axis in modulating the malignant phenotype of CRC cells. Collectively, our data suggest that lncRNA DCST1-AS1 regulates the aggressiveness of CRC cells through hsa-miR-582-5p/HMGB1 axis. Our study provides novel insight into the mechanism of lncRNA DCST1-AS1 in CRC cells for targeted therapy.
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Neoplasias Colorrectales/patología , Proteína HMGB1/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Regulación hacia Arriba , Regiones no Traducidas 5' , Animales , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Células HT29 , Humanos , Ratones , Trasplante de Neoplasias , PronósticoRESUMEN
OBJECTIVE: This study aimed to investigate the potential interactions among long noncoding RNA domain containing 1-antisense (lncRNA DCST1-AS1), miR-21, and periodontal ligament-associated protein-1 (PLAP-1) in periodontitis. BACKGROUND DATA DISCUSSING THE PRESENT STATE OF THE FIELD: It has been verified that miR-21 can target PLAP-1 to regulate the osteogenic differentiation of periodontal ligament cells (PDLCs). METHODS: Differential expression of DCST1-AS1 and miR-21 in PDLCs derived from periodontitis patients and healthy controls was determined by qPCR and unpaired t test. QPCR and Western blots were conducted to evaluate the effects of overexpression of DCST1-AS1 and miR-21 on the expression of PLAP-1. CCK-8 assay was applied to evaluate the effect of DCST1-ASI, miR-21, or PLAP-1 on PDLCs' proliferation. Western blotting was conducted to detect the expression levels of CKD family (CDK4, CDK6, and CCND1). RESULTS: DCST1-AS1 was downregulated in PDLCs derived from periodontitis patients, and its expression was inversely correlated with the expression of miR-2 but positively correlated with PLAP-1. Bioinformatics analysis showed that DCST1-AS1 might bind with miR-21 precursor but not mature miR-21. Transfection experiments showed that overexpression of DCST1-AS1 led to decreased expression levels of miR-21 and significantly increased the expression levels of PLAP-1 at both mRNA and protein levels, while overexpression of miR-21 resulted in a dramatic lower level of PLAP-1. CCK-8 assay indicated that overexpression of DCST1-AS1 or PLAP-1 prohibited PDLCs' proliferation. However, elevation of miR-21 had a contrary effect on the proliferation of PDLCs. And increased expression levels of DCST1-AS1 could significantly inhibit the expression of CDK4, CDK6, and CCND-1, while overexpression of miR-21 inversed the effects of DCST1-AS1. CONCLUSION: Therefore, the expression levels of DCST1-AS1 are much lower in periodontitis patients compared to that in healthy controls, and overexpression of DCST1-AS1 can significantly elevate the expression of PLAP-1 by inhibiting miR-21 in PDLCs.
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MicroARNs , Periodontitis , ARN Largo no Codificante , Proliferación Celular/genética , Proteínas de la Matriz Extracelular , Humanos , MicroARNs/genética , Osteogénesis , Ligamento Periodontal , Periodontitis/genética , ARN Largo no Codificante/genética , Ubiquitina-Proteína LigasasRESUMEN
BACKGROUND: Cervical cancer seriously threatens both the health and life of women. We aimed to investigate whether RNA interference of long non-coding RNA (lncRNA) DCST1-AS1 could promote miR-874-3p expression to affect the proliferation, migration and invasion of cervical cancer cells. METHODS: DCST1-AS1 expression levels in cervical cancer cells and transfection effects were detected by quantitative reverse transcriptase-polymerase chain reaction analysis. Proliferation, invasion and migration of cells were separately shown by cell-counting kit-8, wound healing and transwell assays, and relative protein expression was determined by western blot analysis. Dual-luciferase reporter and RNA immunoprecipitation assays verified the interaction of DCST1-AS1 and miR-874-3p. RESULTS: DCST1-AS1 expression was increased in cervical cancer tissues and cells. The DCST1-AS1 expression in Hela and SiHa cells was the highest, and so the cells were selected for the next experiment. Inhibition of DCST1-AS1 suppressed the proliferation, invasion and migration of cervical cancer cells and decreased the expression of KI67, proliferating cell nuclear antigen, matrix metalloproteinase (MMP)-2 and MMP-9. miR-874-3p expression was increased when cells were transfected with miR-874-3p mimic or shRNA-DCST1-AS1-1, and DCST1-AS1 expression was down-regulated when cells were transfected with miR-874-3p mimic. DCST1-AS1 can directly target miR-874-3p. Furthermore, inhibition of miR-874-3p could effectively alleviate the effect of inhibition of DCST1-AS1 with respect to the proliferation, invasion and migration of cervical cancer cells. CONCLUSIONS: Inhibition of DCST1-AS1 suppressed the proliferation, migration and invasion of cervical cancer cells by increasing miR-874-3p expression, which could be alleviated by the inhibition of miR-874-3p.
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Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Interferencia de ARN , ARN Largo no Codificante/genética , Ubiquitina-Proteína Ligasas/genética , Neoplasias del Cuello Uterino/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Células Cultivadas , Biología Computacional/métodos , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Genes Reporteros , HumanosRESUMEN
INTRODUCTION: LncRNAs have been reported to play critical roles in liver cancer, while its role in other cancers remains unclear. The aim of this study was to investigate the role of DCST1-AS1 in cervical squamous cell carcinoma (CSCC). METHODS: Expression of DCST1-AS1 in CSCC tissues and non-tumor tissues from 68 CSCC patients was determined by RT-qPCR. A 5-year follow-up study was carried out to explore the prognostic value of DCST1-AS1 for CSCC. Overexpression of DCST1-AS1 and miR-107 was achieved in CSCC tissues to explore the interaction between them. The roles of DCST1-AS1, miR-107 and CDK6 in regulating the proliferation and viability of CSCC cells were assessed by cell proliferation and viability assays, respectively. RESULTS: We found that DCST1-AS1 was upregulated in CSCC and predicted poor survival. RNA interaction prediction showed potential interaction between DCST1-AS1 and miR-107. However, overexpression experiments revealed no significant interaction between them. Moreover, overexpression of DCST1-AS1 led to upregulate CDK6 and increase cell proliferation rate, while overexpression of miR-107 played an opposite role and attenuate the effects of overexpression of DCST1-AS1. CONCLUSION: DCST1-AS1 may sponge miR-107 to upregulate CDK6 in CSCC.
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INTRODUCTION: The role of DCST1-AS1 has been investigated in several types of cancer, while the role of DCST1-AS1 in glioblastoma (GBM) is unclear. This study aimed to investigate the role of DCST1-AS1 in GBM. METHODS: GBM and paired non-tumor tissues were collected from 62 GBM patients. Expression levels of DCST1-AS1 and miR-29b in paired tissue samples were determined by RT-qPCR. The role of DCST1-AS1 in regulating the methylation of miR-29b was assessed by methylation-specific PCR (MSP). Cell proliferation was analyzed by cell proliferation assay. RESULTS: It was observed that the upregulation of DCST1-AS1 in GBM predicted poor survival. MiR-29b was downregulated in GBM and inversely correlated with the expression of DCST1-AS1. In GBM cells, overexpression of DCST1-AS1 resulted in the downregulation of miR-29b and the increased methylation level of miR-29b gene. Overexpression of DCST1-AS1 resulted in increased cell proliferation. Moreover, Overexpression of DCST1-AS1 significantly reversed the inhibitory effects of miR-29b on cancer cell proliferation. CONCLUSION: DCST1-AS1 may downregulate miR-29b through methylation in GBM to promote cancer cell proliferation.
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Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , ARN Largo no Codificante/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Metilación de ADN , Regulación hacia Abajo , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Pronóstico , Transfección/métodosRESUMEN
INTRODUCTION: The functions of DCST1-AS1 have been investigated in liver cancer, while its role in endometrial carcinoma (EC) remains hardly known. This study aimed to analyze the role of DCST1-AS1 in EC. METHODS: Paired EC and non-tumor tissue samples were obtained from 62 EC patients. These patients were followed up for 5 years since their admission to record their survival conditions. HEC-1 cells were transfected with DCST1-AS1, Notch1 vectors, miRNA negative control or miR-92a-3p mimic. Luciferase activity was measured. QPCR and Western blot were applied to determine the RNA level and protein expression, respectively. The invasion and migration of HEC-1 cells were analyzed by Transwell assay. RESULTS: We in this study found that DCST1-AS1 was upregulated in EC. Survival analysis revealed that high levels of DCST1-AS1 expression predicted poor survival of EC patients. Bioinformatics analysis revealed that miR-92a-3p may bind DCST1-AS1 and the interaction between them was further confirmed by dual-luciferase activity assay. However, overexpression of miR-92a-3p and DCST1-AS1 failed to affect the expression of each other. Moreover, DCST1-AS1 overexpression led to upregulated Notch1 and increased cancer cell invasion and migration rates. Overexpression of miR-92a-3p played an opposite role and attenuated the effects of DCST1-AS1 overexpression. DISCUSSION: DCST1-AS1 is downregulated in EC and may sponge miR-92a-3p, thereby promoting cancer cell invasion and migration.