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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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NCK1 Antisense RNA 1 (NCK1-AS1), alternatively named as NCK1-DT, is a long non-coding RNA (lncRNA) with important roles in the carcinogenesis. Multiple studies verified its oncogenic role in different types of cancer, including gastric cancer, non-small cell lung cancer, glioma, prostate cancer and cervical cancer. NCK1-AS1 functions as a sponge for several microRNAs, including miR-137, miR-22-3p, miR-526b-5p, miR-512-5p, miR-138-2-3p and miR-6857. In this review we present an outline of NCK1-AS1 function in malignant conditions as well as atherosclerosis.
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Carcinoma de Pulmón de Células no Pequeñas , Glioma , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Masculino , Humanos , ARN sin Sentido/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Glioma/patología , ARN Largo no Codificante/genética , Proliferación Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
Disease development requires the activation of complex multi-factor processes involving numerous long noncoding RNAs (lncRNAs), which describe non-protein-coding RNAs longer than 200 nucleotides. Emerging evidence indicates that lncRNAs act as essential regulators that perform pivotal roles in the pathogenesis and progression of human diseases. The mechanisms underlying lncRNA involvement in diverse diseases have been extensively explored, and lncRNAs are considered powerful biomarkers for clinical practice. The lncRNA noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) antisense 1 (NCK1-AS1), also known as NCK1 divergent transcript (NCK1-DT), is encoded on human chromosome 3q22.3 and produces a 27,274-base-long transcript. NCK1-AS1 has increasingly been characterized as a causative agent for multiple diseases. The abnormal expression and involvement of NCK1-AS1 in various biological processes have been associated with several diseases. Further exploration of the mechanisms through which NCK1-AS1 contributes to disease development and progression will provide a foundation for potential clinical applications of NCK1-AS1 in the diagnosis and treatment of various diseases. This review summarizes the current understanding of the various functions and mechanisms through which NCK1-AS1 contributes to various diseases and the clinical application prospects for NCK1-AS1 (AU)
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Progresión de la Enfermedad , Proliferación Celular , Movimiento Celular , Expresión Génica , Transducción de Señal/genéticaRESUMEN
This study is designed to explore the role of long non-coding RNAs (lncRNAs) NCK1-AS1 in proliferative and invasive activities of esophageal squamous cell carcinoma (ESCC) cells by binding to microRNA-133b (miR-133b) to regulate ENPEP. Differentially expressed lncRNAs, miRs, genes and their targeting relationships were screened on ESCC-related gene expression datasets GSE17351 and GSE6188. The targeting relationships among NCK1-AS1, miR-133b, and ENPEP were verified using functional assays. Loss- and gain- of function assays were carried out to examine the roles of NCK1-AS1, miR-133b, and ENPEP in ESCC cell proliferative, invasive, migrative and apoptotic abilities as well as tumorigenesis in vivo. Elevated NCK1-AS1 and ENPEP but reduced miR-133b expression were found in ESCC. NCK1-AS1 knockdown or miR-133b overexpression inhibited the malignant properties of ESCC cells as well as tumorigenesis in vivo. NCK1-AS1 regulated the ENPEP expression by competitively binding to miR-133b. ENPEP overexpression reversed inhibition of NCK1-AS1 knockdown on the function of ESCC cells. This study provides evidence that silencing NCK1-AS1 inhibits expression of ENPEP by sponging miR-133b, thereby suppressing ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma de Células Escamosas de Esófago/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Esofágicas/metabolismo , Supervivencia Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Carcinogénesis/genética , Regulación Neoplásica de la Expresión Génica/genética , Movimiento Celular/genéticaRESUMEN
Disease development requires the activation of complex multi-factor processes involving numerous long noncoding RNAs (lncRNAs), which describe non-protein-coding RNAs longer than 200 nucleotides. Emerging evidence indicates that lncRNAs act as essential regulators that perform pivotal roles in the pathogenesis and progression of human diseases. The mechanisms underlying lncRNA involvement in diverse diseases have been extensively explored, and lncRNAs are considered powerful biomarkers for clinical practice. The lncRNA noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) antisense 1 (NCK1-AS1), also known as NCK1 divergent transcript (NCK1-DT), is encoded on human chromosome 3q22.3 and produces a 27,274-base-long transcript. NCK1-AS1 has increasingly been characterized as a causative agent for multiple diseases. The abnormal expression and involvement of NCK1-AS1 in various biological processes have been associated with several diseases. Further exploration of the mechanisms through which NCK1-AS1 contributes to disease development and progression will provide a foundation for potential clinical applications of NCK1-AS1 in the diagnosis and treatment of various diseases. This review summarizes the current understanding of the various functions and mechanisms through which NCK1-AS1 contributes to various diseases and the clinical application prospects for NCK1-AS1.
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MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/metabolismo , MicroARNs/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
Increasing evidence demonstrates that many long noncoding RNAs (lncRNAs) are implicated with the development of laryngeal squamous cell carcinoma (LSCC). As shown by bioinformatics analysis, lncRNA non-catalytic region of tyrosine kinase adaptor protein 1-antisense 1 (NCK1-AS1) is upregulated in tissues of head and neck squamous cell carcinoma. The study aimed to explore the role and mechanism of NCK1-AS1 in LSCC. NCK1-AS1 expression in LSCC cells was evaluated by reverse transcription qPCR. The viability, proliferation, invasion, migration, and apoptosis of LSCC cells with indicated transfection were evaluated by CCK-8 assays, Ethynyl deoxyuridine incorporation assays, Transwell assays, wound healing assays, and TUNEL assays, respectively. Subcellular fractionation assays were performed to evaluate the cellular distribution of NCK1-AS1 and NCK1. NCK1 protein level in LSCC cells with indicated transfection was quantified by western blotting. The binding relation between miR-137 and NCK1-AS1 (or NCK1) were determined using RNA immunoprecipitation assays and luciferase reporter assays. NCK1-AS1 was highly expressed in LSCC cell lines. NCK1-AS1 depletion suppressed LSCC cell viability, proliferation, invasion, and migration while enhancing cell apoptosis. NCK1, an adjacent gene of NCK1-AS1, is also highly expressed in LSCC cells and was positively regulated by NCK1-AS1. Moreover, NCK1-AS1 interact with miR-137 to upregulate NCK1 expression. NCK1 was the downstream target of miR-137 and was negatively correlated to miR-137. In addition, overexpressed NCK1 reversed the suppressive impact of NCK1-AS1 depletion on malignant behaviors of LSCC cells. NCK1-AS1 contributes to LSCC cellular behaviors by upregulating NCK1 via interaction with miR-137.
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Neoplasias de Cabeza y Cuello , MicroARNs , ARN Largo no Codificante , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Fenotipo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
BACKGROUND: Although long non-coding RNA (lncRNA) NCK1-AS1 plays important roles in human cancer, its function in atherosclerosis (AS) remains unclear. METHOD: The expression of NCK1-AS1 in AS blood samples was detected by qRT-PCR. Oxidized low-density lipoprotein (ox-LDL) was used to construct the AS cell model, and quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to evaluate NCK1-AS1 level. Cell phenotypes including proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometer, respectively. The malondialdehyde level was measured to evaluate oxidative stress. The expression of apoptosis-related proteins was evaluated by western blot. The expression of inflammatory cytokines (IL-1ß, IL-6 and TNK-α) was measured by qRT-PCR and ELISA assays. The relationship among NCK1-AS1, miR-1197 and COX10 was determined by bioinformatic analysis and luciferase reporter assay. RESULTS: NCK1-AS1 was significantly upregulated in AS blood samples and ox-LDL stimulated vascular smooth muscle cells (VSMCs). Knockdown of NCK1-AS1 increased cell viability, reduced cell apoptosis and MDA level, and also inhibited the expression of inflammatory cytokines (IL-1ß, IL-6 and TNK-α) in ox-LDL stimulated VSMCs. NCK1-AS1 could positively regulate COX10 expression by directly sponging miR-1197. Moreover, co-transfection of sh-NCK1-AS1 and miR-1197 inhibitor, or co-transfection of sh-NCK1-AS1 and pc-COX10 (COX10 overexpressing plasmid) obviously reduced cell viability, promoted cell apoptosis, and increased MDA level in VSMCs followed by ox-LDL treatment for 24 h compared to that in sh-NCK1-AS1 transfected VSMCs. CONCLUSION: Our study revealed that knockdown of NCK1-AS1 attenuated the development of AS by regulating miR-1197/COX10 axis, suggesting that this lncRNA might be a potential therapeutic target for AS.
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BACKGROUND: Long non-coding RNAs (lncRNAs) are vital regulators of gene expression and cellular processes in multiple cancers, including melanoma. Nevertheless, the function of lncRNA NCK1-antisense 1 (NCK1-AS1) in melanoma remains unknown. METHODS: RT-qPCR was used to analyze the expression of NCK1-AS1, microRNA-526b-5p (miR-526b-5p) and ADAM metallopeptidase domain 15 (ADAM15). Cell proliferation was determined by CCK-8, colony formation and EdU assays. Cell migration was assessed by transwell migration and wound healing assays. Mechanism experiments including luciferase reporter, RIP and RNA pull down assays were conducted to demonstrate the interactions between RNAs. Xenograft model was established to verify the function of NCK1-AS1 and miR-526b-5p in melanoma in vivo. RESULTS: NCK1-AS1 was overexpressed in melanoma cell lines and NCK1-AS1 knockdown hampers the proliferation and migration of melanoma cells. Besides, miR-526b-5p binds to NCK1-AS1 in melanoma and ADAM15 was validated as its downstream target. Further, the inhibitory effects of NCK1-AS1 knockdown on cell proliferation and migration in melanoma were reversed by the depletion of miR-526b-5p and further counteracted by ADAM15 knockdown. The growth of melanoma tumors was hindered by the down-regulation of NCK1-AS1 or up-regulation of miR-526b-5p. CONCLUSION: NCK1-AS1 facilitates cell proliferation and migration in melanoma via targeting miR-526b-5p/ADAM15 axis.
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This paper aimed at investigating AS1 expression in prostate cancer (PCa) and its effects on the proliferation and invasion of prostate cancer cells (PCCs). The prostate tissues and the matched adjacent normal prostate tissues excised and preserved during radical prostatectomy in our hospital were collected. The LncRNA NCK1-AS1 expression was detected. PCa patients were followed up for three years to analyze their prognosis. The correlation of LncRNA NCK1-AS1 expression with clinicopathological features was analyzed. Human normal prostate cells and human PCCs were selected, in which LncRNA NCK1-AS1 expression was tested to screen and then transfect the cells. Cell proliferation, invasion and migration were detected. Cell cycles and apoptosis were analyzed. Compared with the adjacent normal tissues, LncRNA NCK1-AS1 was highly expressed in the prostate cancer tissues. Its expression was remarkably different in those with different stages of TNM and with lymphatic metastasis or not. The prognosis of patients with high LncRNA NCK1-AS1 expression was remarkably poorer than that of those with low expression. Compared with the human normal prostate cells, LncRNA NCK1-AS1 expression in the human PCCs remarkably rose, with the greatest difference in 22Rv1 cells. Compared with the Blank group, cell proliferation and the number of plate cloned cells remarkably reduced in the sh-NCK1-AS1 group. Additionally, in this group, the number of invasive and migratory cells remarkably reduced; the expression of invasion-related protein E-cadherin remarkably rose but that of MMP-2 remarkably reduced; cell cycles were arrested and the expression of cycle-related proteins (CDK4, CDK6, cyclin D1) remarkably reduced; the apoptotic rate and the expression of apoptosis-related protein Bax remarkably rose. LncRNA NCK1-AS1 is highly expressed in PCa, so its down-regulation can inhibit PCCs from proliferating and reduce the number of invasive cells.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Oncogénicas/metabolismo , Neoplasias de la Próstata/fisiopatología , Anciano , Proliferación Celular , Humanos , Masculino , Invasividad Neoplásica , TransfecciónRESUMEN
Long noncoding RNAs (lncRNAs) exert crucial effects on the development of many malignancies, including gastric cancer. Herein, we investigated the role of lncRNA noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) divergent transcript (NCK1-DT, also known as NCK1-AS1) in gastric cancer. Reverse transcription quantitative polymerase chain reaction demonstrated that NCK1-AS1 exhibited high expression in gastric cancer tissues and cells. In vitro assays including MTT, colony formation, Transwell, wound healing and sphere formation assays indicated that NCK1-AS1 depletion inhibited cell proliferation, migration, invasion and stemness maintenance. Luciferase reporter and RIP assays suggested that NCK1-AS1 functioned as a competitive endogenous RNA (ceRNA) for miR-22-3p to positively modulate BCL9 expression. BCL9 was a target gene of miR-22-3p. According to western blot analysis and TOP/FOP flash assay, NCK1-AS1 activated the Wnt/ß-catenin signaling via the miR-22-3p/BCL9 axis. Furthermore, rescue experiments verified that NCK1-AS1 affected cellular processes by activating the Wnt/ß-catenin signaling pathway via the miR-22-3p/BCL9 axis. Tumor xenograft model validated that NCK1-AS1 promoted tumor growth in vivo via the Wnt/ß-catenin signaling by upregulating BCL9 expression. Overall, NCK1-AS1 functions as an oncogene and promotes gastric cancer progression via the miR-22-3p/BCL9-Wnt/ß-catenin signaling pathway.
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MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Proteínas Adaptadoras Transductoras de Señales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Oncogénicas , Oncogenes , Factores de Transcripción , Vía de Señalización Wnt , beta Catenina/metabolismoRESUMEN
Lung squamous cell carcinoma (LUSC) is a prevalent subtype of nonsmall cell lung cancer (NSCLC). Dysregulated long noncoding RNAs (lncRNAs) are increasingly identified as pivotal modulators in cancer progression. NCK1 divergent transcript (NCK1-AS1) is a lncRNA that has been proven to be oncogenic in different types of human cancers. However, whether it exerts similar functions in LUSC remains to be elusive. The present study focused on investigating the influence of NCK1-AS1 on the cellular process in LUSC and exploring its underlying mechanism. Through online bioinformatics analysis, we obtained a high NCK1-AS1 level in LUSC tissues. Meanwhile, we confirmed that NCK1-AS1 was upregulated in LUSC cells. Gain- or loss-of-function assays suggested that NCK1-AS1 prompted cell proliferation and migration, whilst impeded cell apoptosis in LUSC. Mechanistically, we revealed that NCK1-AS1 induced the upregulation of its nearby gene NCK adaptor protein 1 (NCK1) at the transcriptional level by interacting with the transcription factor MYC proto-oncogene (MYC). Rescue assays indicated that NCK1 participated in the regulation of NCK1-AS1 on LUSC progression. In conclusion, we firstly demonstrated the oncogenic role of NCK1-AS1 in LUSC and illustrated its downstream molecular mechanism.
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Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Proteínas Oncogénicas/genética , Proteínas Proto-Oncogénicas c-myc/genética , ARN Largo no Codificante/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/fisiología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Largo no Codificante/metabolismo , Activación Transcripcional , Transfección , Regulación hacia ArribaRESUMEN
Long noncoding RNAs (lncRNAs) have been shown to play important roles in carcinogenesis and progression. In this study, we mainly investigate the potential influence of lncRNA NCK1 antisense RNA 1 (NCK1-AS1) on the progression of non-small cell lung cancer (NSCLC). RT-PCR was performed to determine the expression of NCK1-AS1 and miR-137 in NSCLC specimens and cell lines. The clinical significance of NCK1-AS1 in 148 patients was analyzed statistically. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of NCK1-AS1 and miR-137. Regulatory effects of NCK1-AS1 on proliferative, colony formation abilities, metastasis and apoptosis of SK-MES-1 and H1299 cells were assessed through a series of functional experiments. RNA-pull down and Dual-Luciferase reporter assay was performed to verify the sponge effect of NCK1-AS1 on miR-137. We observed that NCK1-AS1 expression was upregulated, while miR-137 expression was down-regulated in NSCLC specimens and cell lines. Increased NCK1-AS1 expression was positively correlated with TNM stage and lymph node metastasis and poor clinical outcome. The diagnostic value of NCK1-AS1 and miR-137 expression was also confirmed. Functionally, knockdown of NCK1-AS1 suppressed the proliferation, migration and invasion of NSCLC cells, and promoted apoptosis. Moreover, NCK1-AS1 was able to adsorb miR-137 via a sponge effect. Overall, our findings suggested that NCK1-AS1 may be a candidate biomarker and a target for new therapies in NSCLC patients.
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BACKGROUND: Oral squamous cell carcinoma (OSCC) at early stages can be misdiagnosed as an oral ulcer (OU) due to similar symptoms, such as chronic and indurated ulcer. LncRNA NCK1-AS1 has been characterized as a key player in cervical cancer, while its role in OSCC is unknown. METHODS: All participants were selected at Jiangxi Province Tumor Hospital from December 2016 to December 2018. Expression levels of NCK1-AS1 and miR-100 in plasma from both OSCC and OU patients were measured by RT-qPCR. Diagnostic analysis was performed through ROC curve. Potential interactions between NCK1-AS1 and miR-100 were detected by cell transfection experiments. Cell invasion and migration were assessed by Transwell assays. RESULTS: The expression of NCK1-AS1 was upregulated in early-stage OSCC patients but not in OU patients. Upregulation of NCK1-AS1 distinguished OSCC patients from OU patients. The expression of miR-100 was inversely correlated with the expression of NCK1-AS1. Overexpression of NCK1-AS1 was followed by promoted OSCC cell invasion and migration. Overexpression of miR-100 did not affect the expression of NCK1-AS1 but inhibited the role of NCK1-AS1. CONCLUSIONS: Therefore, NCK1-AS1 may promote the metastasis of OSCC by downregulating miR-100.
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INTRODUCTION: Long non-coding RNA (lncRNA) NCK1-AS1 could regulate multiple cancer progression. However, little is known regarding the roles and acting mechanisms of NCK-AS1 in gastric cancer (GC) progression. This work was aimed to explore the relationship between NCK1-AS1 and GC progression to illustrate the mechanisms of NCK1-AS1. METHODS: NCK1-AS1 expression level in GC tissues and cells was measured with a quantitative real-time PCR method. In vitro experiments including cell counting kit-8 assay, colony formation assay, wound-healing assay, and transwell invasion assay were employed to detect biological roles of NCK1-AS1 in GC progression. In vivo experiments were performed to analyze the roles of NCK1-AS1 on GC malignant phenotype. Moreover, mechanisms behind the biological roles of NCK1-AS1 in GC were investigated using bioinformatic analysis, luciferase activity reporter assay, RNA immunoprecipitation assay, and rescue experiments. RESULTS: NCK1-AS1 was found to have elevated expression in GC tissues and cells in comparison with normal counterparts. Loss-of-function experiments showed knockdown of NCK1-AS1 refrained GC cell proliferation, colony formation, migration, and invasion in vitro. Animal experiments showed silence of NCK1-AS1 suppresses tumor growth in vivo. Functionally, NCK1-AS1 serves as a sponge for microRNA-137 (miR-137) to upregulate nucleoporin 43 (NUP43) expression in GC. Rescue experiments proved the carcinogenic role of NCK1-AS1/miR-137/NUP43 axis in GC progression. DISCUSSION: In conclusion, the NCK1-AS1/miR-137/NUP43 axis was identified that could contribute to GC malignancy behaviors.
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Glioma is the deadliest disease in human central nerve system. Abnormal expression of long noncoding RNA (lncRNA) expression has been demontrated to be implicated in various cancers. The oncogenic role of lncRNA NCK1-AS1 has been validated in cervical cancer, wheras its role in glioma remians obscure. Our research findings suggested that NCK1-AS1 was upregulated in glioma tissues and cells. NCK1-AS1 deficiency hindered cell proliferation and enhanced cell apoptosis. Additionally, the chemoresistance and radioresistance of glioma cells were impaired by NCK1-AS1 depletion. Moreover, miR-22-3p, a downstream gene of NCK1-AS1, could weaken glioma cell chemoresistance and radioresistance. Similarly, IGF1R was the downstream target gene of miR-22-3p. Further mechanism and function assays demonstrated that NCK1-AS1 promoted glioma cell growth, chemoresistance and radioresistance via sponging miR-22-3p to upregulate IGF1R. Finally, the tumor facilitator function of NCK1-AS1 was also verified by in vivo experiments. Taken together, NCK1-AS1 contributes to glioma cell proliferation, radioresistance and chemoresistance via miR-22-3p/IGF1R ceRNA pathway, which might provide a new insight for improving the radiotherapy and chemotherapy treatments of glioma.
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Neoplasias Encefálicas/patología , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Glioma/patología , MicroARNs/metabolismo , ARN Largo no Codificante/genética , Receptor IGF Tipo 1/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de la radiación , Glioma/genética , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Proteínas Oncogénicas/genética , Receptor IGF Tipo 1/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: This study aimed at probing into the effect of lncRNA NCK1-AS1 on proliferation, migration and invasion of non-small cell lung cancer (NSCLC) cells and its regulatory function on miR-512-5p/p21 molecular axis. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the expressions of NCK1-AS1 and miR-512-5p in NSCLC tissues and cell lines. The alterations of cell proliferation, migration, invasion and cell cycle were examined by cell counting kit-8 (CCK-8) assay, BrdU experiment, Transwell experiment and flow cytometry, respectively. The dual-luciferase reporter assay and RNA immunoprecipitation experiment were performed to validate the binding relationships between miR-512-5p and NCK1-AS1, and miR-512-5p the 3'UTR of p21 mRNA. Western blot was used to determine the effects of NCK1-AS1 and miR-512-5p on p21 protein expression. RESULTS: NCK1-AS1 expression was up-regulated in NSCLC tissues and cells, and its high expression was correlated with shorter overall survival time and faster progression of patients. Overexpression of NCK1-AS1 promoted NSCLC cell proliferation, migration and invasion, and accelerated the cell cycle, whereas NCK1-AS1 siRNA inhibited these malignant biological behaviors, and arrested cell cycle. NCK1-AS1 could bind to miR-512-5p, p21 was verified as a target gene of miR-512-5p, and NCK1-AS1 could up-regulate the expression of p21 in NSCLC cells via repressing miR-512-5p expression. CONCLUSION: NCK1-AS1 promotes NSCLC progression by regulating miR-512-5p/p21 molecular axis.
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Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , MicroARNs/genética , Proteínas Oncogénicas/genética , ARN sin Sentido/genética , ARN Largo no Codificante/genética , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Glioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms. METHODS: Microarray analyses were performed to explore the lncRNAs/miRNAs/genes with differential expression in glioma. NCK1-AS1 levels in glioma tissues and normal brain tissues, and in glioma cell lines and normal human glial cells were identified. The interactions among NCK1-AS1, miR-138-2-3p and TRIM24 were validated through luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Gain- and loss-of functions of NCK1-AS1, miR-138-2-3p and TRIM24 were performed to identify their roles in the behaviors of glioma cells. The activity of the Wnt/ß-catenin pathway was measured. In vivo experiments were performed as well. RESULTS: High expression of NCK1-AS1 was found in glioma tissues and cells, especially in U251 cells. Online predictions and the integrated experiments identified that NCK1-AS1 elevated the TRIM24 expression through sponging miR-138-2-3p, and further activated the Wnt/ß-catenin pathway. Artificial silencing of NCK1-AS1 or up-regulation of miR-138-2-3p led to inhibited proliferation, invasion and migration but promoted cell apoptosis of U251 cells, while up-regulation of TRIM24 reversed these changes, and it activated the Wnt/ß-catenin pathway. The in vitro results were reproduced in in vivo experiments. CONCLUSIONS: Our study suggested that NCK1-AS1 might elevate TRIM24 expression and further activate the Wnt/ß-catenin pathway via acting as a ceRNA for miR-138-2-3p. Silencing of NCK1-AS1 might inhibit the progression of glioma.
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Proteínas Portadoras/genética , Glioma/genética , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , beta Catenina/metabolismo , Animales , Carcinogénesis , Femenino , Humanos , Ratones , Ratones Desnudos , TransfecciónRESUMEN
BACKGROUND: Long noncoding RNAs (lncRNAs) play critical and complex roles in regulating various biological processes of cancers. Our study aimed to investigate the involvement of lncRNA NCK1-AS1 in urinary bladder cancer (UBC). METHODS: qRT-PCR was used to detect the expression of lncRNA NCK1-AS1 and miR-143 in UBC tissues and cells. The dual-luciferase reporter system assays were used to confirm the interaction between NCK1-AS1 and miR-143, and flow cytometry assays were applied to examine the behavioral changes in HT-1376 and HT-1197 cell lines. RESULTS: It was observed that NCK1-AS1 was up-regulated, while miR-143 was down-regulated in tumor tissues than in adjacent healthy tissues of urinary bladder cancer (UBC) patients. A 5-year survival analysis showed that the survival rate of patients with high NCK1-AS1 level or low miR-143 level in tumor tissues appears relatively low. Correlation analysis revealed a significant inverse correlation between NCK1-AS1 and miR-143 in tumor tissues. Over-expression NCK1-AS1 reduced the expression level of miR-143, while elevating the level of miR-143 failed to affect NCK1-AS1 expression. NCK1-AS1 over-expression led to promoted proliferation and increased percentage of CD133+ (stemness) cells. CONCLUSION: Therefore, NCK1-AS1 promotes cancer cell proliferation and increases cell stemness in UBC patients by down-regulating miR-143.
RESUMEN
Long non-coding RNAs (lncRNAs) have been unveiled to play crucial parts in tumorigenesis and chemo-resistance of multiple cancers. Herein, we explored the role of NCK1-AS1 in ovarian cancer (OC). As indicated by TCGA, NCK1-AS1 was markedly upregulated in OC tissues. Besides, we found a dramatic upregulation of NCK1-AS1 in OC cell lines relative to the normal IOSE cells. Interestingly, silencing NCK1-AS1 confined cell proliferation, induced apoptosis and suppressed migration and invasion as well as enhanced DDP sensitivity in OC cells. As for mechanistic investigation, starBase (http://starbase.sysu.edu.cn/) suggested that NCK1-AS1 expression in OC tissues was significantly positively correlated with its adjacent gene, NCK adaptor protein 1 (NCK1). Furtherly, we demonstrated that the cytoplasmic NCK1-AS1 competed with NCK1 mRNA for miR-137 binding to boost NCK1 mRNA expression. Importantly, miR-137 inhibition could only offset the suppression of NCK1-AS1 depletion on NCK1 mRNA level but not the protein level. Moreover, NCK1-AS1 stabilized NCK1 protein by hindering c-Cbl-induced degradation via directly interacting with c-Cbl. Furthermore, NCK1 upregulation reversed the influences of NCK1-AS1 inhibition on the biological behaviors and DDP resistance of OC cells. This study disclosed a NCK1-AS1/NCK1 axis in regulating OC progression and chemo-resistance, opening a new path for treatment and chemo-resistance overcoming in OC.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Carcinogénesis/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Oncogénicas/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , ARN Largo no Codificante/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular/genética , Cisplatino/farmacología , Cisplatino/uso terapéutico , Progresión de la Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica , Proteínas Oncogénicas/metabolismo , Neoplasias Ováricas/patología , Proteolisis , Proteínas Proto-Oncogénicas c-cbl/metabolismo , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
Background: Glioma is a common malignant tumor. The purpose of this study was to investigate the effect and molecular mechanism of long noncoding RNA (lncRNA) NCK1-AS1 on the drug resistance of temozolomide (TMZ) in glioma cells. Methods: The fresh and recurrent glioma tissues and peritumoral brain edema (PTBE) were collected from the same patient. U251 and A172 cells were treated with TMZ to screen TMZ-resistant cells. The expression levels of NCK1-AS1, miR-137, or TRIM24 were detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, in situ hybridization (ISH), or RNA pull-down assay. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazoliumbromide (MTT) assay. In addition, the relationship between NCK1-AS1 and miR-137 or TRIM24 and miR-137 was confirmed by dual luciferase activity assay. Results: NCK1-AS1 expression was increased in regular and recurrent glioma tissues and TMZ-resistant cells. Cell viability was increased in TMZ-resistant cells, and the IC50 of TMZ also increased in TMZ resistant cells. However, knockdown of NCK1-AS1 inhibited these increases. Moreover, suppression of NCK1-AS1 increased miR-137 expression, whereas overexpression of miR-137 decreased TRIM24 expression. Then, expression of miR-137 alleviated the NCK1-AS1 overexpression-induced increased expression of TRIM24. In addition, the decreases of cell viability and IC50 induced by NCK1-AS1 knockdown were reversed after adding TRIM24 in U251/TMZ and A172/TMZ cells. Conclusion: NCK1-AS1 could increase drug resistance of glioma cells to TMZ by modulating miR-137/TRIM24 pathway.