RESUMEN

BACKGROUND: Non-small lung cancer ranks first in the cancer-related death of all malignant tumors. Exploring novel biological targets is of great significance for diagnosis and therapy of NSCLC. OBJECTIVE: In this study, we aimed to explore the effect of LINC00668 on the biological functions of NSCLC cells and the underlying mechanism. METHODS: RT-qPCR assays and western blot assays were utilized to estimate the relative gene expression at mRNA and protein levels, respectively. CCK8, colony formation, wound healing, transwell, and cell apoptosis assays were employed to assess cell function. IHC and FISH assays were used to determine the gene expression in NSCLC tissues. RIP and dual-luciferase assays were conducted to validate the combination between LINC00668 and miR-518c-3p. The correlation of expression between miR-518c-3p and LINC00668 or TRIP4 was determined by Pearson correlation analysis. RESULTS: LINC00668 was aberrantly upregulated in NSCLC tumor tissues and cell lines. Inhibition of LINC00668 significantly suppressed tumor proliferation, migration, invasion and promoted cell apoptosis. Mechanistically, LINC00668 could bind to miR-518c-3p, thus targeting the 3'UTR of TRIP4. TRIP4 overexpression rescued the weakened cell function mediated by LINC00668 silencing. CONCLUSIONS: LINC00668 acted as an oncogene in NSCLC progression through miR-518c-3p/TRIP4 axis. Our study disclosed a new mechanism of LINC00668 functioned in NSCLC and may give a deeper insight of the targeted therapy of NSCLC in the future.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo

RESUMEN

Epidemiological studies show an association between inflammatory bowel disease (IBD) and increased risk of thrombosis. However, how IBD influences thrombosis remains unknown. The current study shows that formation of neutrophil extracellular traps (NETs) significantly increased in the dextran sulfate sodium (DSS)-induced IBD mice, which in turn, contributes to thrombus formation in a NETs-dependent fashion. Furthermore, the exosomes isolated from the plasma of the IBD mice induce arterial and venous thrombosis in vivo. Importantly, proinflammatory factors-exposed intestinal epithelial cells (inflamed IECs) promote neutrophils to release NETs through their secreted exosomes. RNA sequencing revealed that LINC00668 is highly enriched in the inflamed IECs-derived exosomes. Mechanistically, LINC00668 facilitates the translocation of neutrophil elastase (NE) from the cytoplasmic granules to the nucleus via its interaction with NE in a sequence-specific manner, thereby inducing NETs release and thrombus formation. Importantly, berberine (BBR) suppresses the nuclear translocation of NE and subsequent NETs formation by inhibiting the interaction of LINC00668 with NE, thus exerting its antithrombotic effects. This study provides a novel pathobiological mechanism linking IBD and thrombosis by exosome-mediated NETs formation. Targeting LINC00668 can serve as a novel molecular treatment strategy to treat IBD-related thrombosis.

Asunto(s)

Exosomas , Trampas Extracelulares , Enfermedades Inflamatorias del Intestino , Trombosis , Animales , Ratones , Trombosis/etiología , Neutrófilos

RESUMEN

Cell cycle regulation is an important cellular function. Abnormal regulation of this process can cause cancer. Several genes are involved in this process. There is no comprehensive study on expression pattern of cell cycle related lncRNAs in breast cancer patients. In the current study, we evaluated expressions of LINC00668, PRDM16-DT, SNHG7 and CDKN2A in 42 pairs of breast cancer tissues and adjacent non-tumoral tissues. Expression of SNHG7 was significantly lower in tumoral tissues compared with non-tumoral tissues. However, expressions of LINC00668, PRDM16-DT and CDKN2A were not significantly different between these two sets of samples. Expression levels of SNHG7 could separate tumoral tissues from non-tumoral tissues with AUC value= 0.66, sensitivity= 61% and specificity= 73%. Expression of CDKN2A was associated with clinical stage (P value=0.01). Expression levels of LINC00668, PRDM16-DT, SNHG7 and CDKN2A were higher in estrogen receptor (ER) positive samples compared with ER negative ones (P values=0.044, 0.008, 0.002 and 0.022, respectively). Moreover, expression of SNHG7 was higher in progesterone receptor (PR) positive samples compared with PR negative ones (P value=0.02). Finally, expressions of PRDM16-DT, SNHG7 and CDKN2A were higher in HER2/neu positive samples compared with HER2/neu negative ones (P values=0.017, 0.02 and 0.021, respectively). Taken together, our study demonstrates possible roles of these genes in breast cancer and warrants further functional studies.

Asunto(s)

Neoplasias de la Mama , ARN Largo no Codificante , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica/genética

RESUMEN

BACKGROUND: A lack of effective treatment for lung squamous cell carcinoma (LUSC) makes it an important factor restricting the 5-year survival rate of non-small cell lung cancer (NSCLC). Long non-coding RNA 00668 (LINC00668) was reported to play crucial regulatory roles in the tumorigenesis and progression of various cancers; however, its role in LUSC is unclear. The aim of this study was to investigate the prognosis value and biological function of LINC00668 in NSCLC, especially in LUSC. METHODS: The expression pattern of LINC00668 and its relationship with clinical characteristics and prognosis of patients were investigated in the NSCLC especially LUSC based on The Cancer Genome Altas (TCGA) database. Its function in LUSC cells was explored in vitro. RESULTS: LINC00668 expression was significantly up-regulated in LUSC patients and high expression level of LINC00668 was associated with advanced tumor-node-metastasis (TMN) stage. Moreover, the expression of LINC00668 significantly increased in smoking patients, and was a prognostic indicator for overall survival (OS) of smoking patients with LUSC. In vitro experiments showed that LINC00668 has significantly higher expression level in LUSC cell lines and tissues compared to normal bronchial epithelial cell and para-tumor tissues; meanwhile, functional assay indicated knockdown of LINC00668 effectively inhibited the migration and invasion of LUSC cells. CONCLUSIONS: LINC00668 might closely relate to the development of LUSC, and inhibition of LINC00668 may reduce the metastasis of LUSC.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , ARN Largo no Codificante , Carcinoma de Células Escamosas/genética , Movimiento Celular/genética , Humanos , Pulmón , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética

RESUMEN

BACKGROUND@#A lack of effective treatment for lung squamous cell carcinoma (LUSC) makes it an important factor restricting the 5-year survival rate of non-small cell lung cancer (NSCLC). Long non-coding RNA 00668 (LINC00668) was reported to play crucial regulatory roles in the tumorigenesis and progression of various cancers; however, its role in LUSC is unclear. The aim of this study was to investigate the prognosis value and biological function of LINC00668 in NSCLC, especially in LUSC.@*METHODS@#The expression pattern of LINC00668 and its relationship with clinical characteristics and prognosis of patients were investigated in the NSCLC especially LUSC based on The Cancer Genome Altas (TCGA) database. Its function in LUSC cells was explored in vitro.@*RESULTS@#LINC00668 expression was significantly up-regulated in LUSC patients and high expression level of LINC00668 was associated with advanced tumor-node-metastasis (TMN) stage. Moreover, the expression of LINC00668 significantly increased in smoking patients, and was a prognostic indicator for overall survival (OS) of smoking patients with LUSC. In vitro experiments showed that LINC00668 has significantly higher expression level in LUSC cell lines and tissues compared to normal bronchial epithelial cell and para-tumor tissues; meanwhile, functional assay indicated knockdown of LINC00668 effectively inhibited the migration and invasion of LUSC cells.@*CONCLUSIONS@#LINC00668 might closely relate to the development of LUSC, and inhibition of LINC00668 may reduce the metastasis of LUSC.

Asunto(s)

Humanos , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas/genética , Movimiento Celular/genética , Pulmón , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética

RESUMEN

In China, gastric cancer (GC) ranks first in the incidence of all malignant tumors. With high recurrence and distant metastasis, GC has caused considerable mortalities. LncRNA long intergenic non-protein-coding RNA 668 (LINC00668) has been reported to be upregulated in GC cells and predict poor prognosis of GC patients. However, the mechanism of LINC00668 has not been fully investigated in GC. This study aimed to investigate the role of LINC00668 in GC. We found that LINC00668 level was upregulated in GC tissue and cells and predicted poor prognosis. Functionally, LINC00668 knockdown suppressed GC cell migration and invasion. Additionally, LINC00668 knockdown inhibited epithelial to mesenchymal transition (EMT) process. PKN2 exerts similar effects with LINC00668 in GC cells. LINC00668 knockdown suppressed tumor growth and metastasis in vivo. Mechanistically, HuR was predicted to bind with LINC00668 and protein kinase N2 (PKN2). RNA pull-down assays validated the binding between HuR and LINC00668 (or PKN2). Moreover, either silencing of LINC00668 or HuR could decrease PKN2 mRNA stability or reduce PKN2 mRNA and protein levels. Furthermore, PKN2 expression was positively correlated with LINC00668 expression and HuR expression in GC tissues, and HuR expression was positively associated with LINC00668 expression in GC tissues. Finally, rescue assays confirmed that the suppressive effect of LINC00668 silencing on cell migration, invasion, and EMT process was reversed by PKN2 overexpression or HuR upregulation. In conclusion, LINC00668 cooperated with HuR-dependent upregulation of PKN2 to facilitate gastric cancer metastasis, which may provide a potential novel insight for GC treatment.

Asunto(s)

ARN Largo no Codificante , Neoplasias Gástricas , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Proteína 1 Similar a ELAV , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica , Proteína Quinasa C , ARN Largo no Codificante/genética , Neoplasias Gástricas/genética , Regulación hacia Arriba

RESUMEN

Liver cancer is now one of the most lethal and commonest cancers in the world, among which over 90% is hepatocellular carcinoma (HCC). Recent studies have confirmed long non-coding RNAs (lncRNAs) are implicated in carcinogenesis. It has been reported lncRNA LINC00668 serves as an oncogene in several cancers. However, the mechanism where LINC00668 regulates HCC is still unclear. qRT-PCR analysis was adopted to detect the expression of relative RNAs. Cytoplasmic and nuclear RNA fraction analysis was conducted to verify the underlying molecular mechanism. Cell colony formation was carried out to test cell colony formation ability and transwell assays were performed to testify cell migratory and invaded abilities. Relevant protein expression level was measured by Western blot assay. LINC00668 was significantly up-regulated in HCC tissues and cell lines. LINC00668 knockdown inhibited cell proliferative, migratory and invasion abilities and slowed down the epithelial-mesenchymal transition (EMT) process. Mechanistically, LINC00668 positively modulates the expression of YY1 by competitively binding to miR-532-5p. It was revealed that LINC00668 up-regulation accelerated cell proliferation and motility in HCC and suggested LINC00668 could be a potential therapeutic target for HCC.

Asunto(s)

Carcinoma Hepatocelular/metabolismo , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Factor de Transcripción YY1/metabolismo , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , ARN Largo no Codificante/genética , Transducción de Señal , Carga Tumoral , Factor de Transcripción YY1/genética

RESUMEN

Glioma is a common invasive cancer with unfavorable prognosis in patients. Long non-coding RNAs (lncRNAs) exert significant functions in carcinogenesis of various cancers including glioma. Among them, long intergenic non-coding RNA 668 (LINC00668) was reported to function as oncogene in various cancers, but its molecular mechanism in glioma has not been thoroughly researched. Our current study aimed to investigate the role and molecular mechanism of LINC00668 in glioma cells. We initially found out that LINC00668 was up-regulated in glioma cells. Through a series of function assays, LINC00668 was verified to facilitate cell proliferation and inhibit apoptosis in glioma. Then, by means of online databases, RNA pull down assay and RIP assay, we verified the binding relation between LINC00668 and miR-518c-3p. Also, the next function assays exposed that miR-518c-3p was the tumor suppressor in glioma cells. Similarly, SOCS5 (suppressor of cytokine signaling 5) was found to bind with miR-518c-3p, which repressed glioma tumorigenesis by targeting SOCS5. Moreover, rescue assays manifested that LINC00668 modulated expression of SOCS5 in a miR-518c-3p-dependent way and further regulated glioma tumorigenesis. Overall, LINC00668 modulates SOCS5 expression through competitively sponging miR-518c-3p to facilitate glioma cell proliferation.

Asunto(s)

Neoplasias Encefálicas/metabolismo , Proliferación Celular/fisiología , Glioma/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/biosíntesis , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , Proteínas Supresoras de la Señalización de Citocinas/genética

RESUMEN

Objective: To elucidate how lncRNA 00668 (LINC00668) influences the development of breast cancer (BC). Materials and methods: Genome-wide expression profile of BC and paracancerous tissues were downloaded from The Cancer Genome Atlas (TCGA) and BC tissues and paracancerous tissues enrolled from our hospital for analyzing the expression level of LINC00668 and its correlation with prognosis. GSEA was conducted to analyze the potential functions of LINC00668. By transfection of sh-LINC00668 in BC cells, proliferation, apoptosis, cell cycle and colony formation of BC cells were accessed. Western blot was conducted to detect protein expressions of Ki-67, CDK4, Bcl-2, p21 and genes in AKT/mTOR pathways after LINC00668 knockdown in BC cells. Finally, tumor-bearing nude mice were administrated with BC cells. We compared the proliferative rate in mice with different administrations. Immunohistochemistry was carried out to access expression levels of Ki-67, CDK4, Bcl-2 and P21 in mice. Results: Both TCGA data and BC tissues harvested from our hospital indicated the higher expression of LINC00668 in BC tissues. LINC00668 expression was negatively correlated to prognosis of BC patients. GSEA pointed out that LINC00668 is enriched in regulations of cell cycle and apoptosis. By transfection of sh-LINC00668 in MDA-MB-231 and MDA-MB-436 cells, the proliferative and colony formation abilities of BC cells decreased. Besides, LINC00668 knockdown in BC cells induced apoptosis and arrested cell cycle. LINC00668 knockdown downregulated Ki-67, CDK4 and Bcl-2, but upregulated p21. The AKT/mTOR pathway was inhibited after LINC00668 silenced. In vivo experiments demonstrated the decreased proliferative rate in tumor-bearing mice administrated with sh-LINC00668 transfected BC cells. Consistently, immunohistochemical results showed lower positive expressions of Ki-67, CDK4 and Bcl-2, but higher positive expression of p21 in sh-LINC00668 group. Conclusion: LINC00668 is highly expressed in BC tissues and can promote the progression of BC by inhibiting apoptosis and accelerating cell cycle progression.

RESUMEN

Ophiopogonin-B (OP-B) has been reported to suppress metastasis and angiogenesis of adenocarcinoma A549 cells in vitro and in vivo. More and more evidences indicate that inflammatory microenvironment facilitates tumor metastasis. Digital Gene Expression (DGE) analysis of non-small cell lung cancer (NSCLC) cell lines showed that OP-B downregulated the expression of linc00668, which promoted progression of cancer. Herein, we simulated the inflammatory microenvironment by co-culturing A549 cells with LPS-treated THP-1 cells and found that the level of linc00668 increased significantly in the mock group, while OP-B treatment inhibited the level of linc00668 and reversed epithelial-mesenchymal transition (EMT) induced by linc00668. In addition, overexpression of linc00668 in A549 cells suppressed the expression of E-cadherin and induced expression of N-cadherin, while OP-B treatment reversed these changes. Bioinformatic prediction and dual-luciferase reporter gene assay validated that linc00668 sponge miR-432-5p and at last acted on EMT to execute the anti-migration function of A549 cells under inflammatory microenvironment. Taken together, OP-B inhibits metastasis of A549 cells via the linc00668/miR-432-5p/EMT axis.

RESUMEN

Long intergenic non-coding RNA No.668 (LINC00668) is implicated in the development of various malignancies. However, the role of LINC00668 and underlying mechanism in colorectal cancer (CRC) remains totally unknown. The expression pattern of LINC00668 in CRC cells were determined by qRT-PCR. CCK-8, EdU incorporation, flow cytometry, Transwell, and wound-healing assays were run to evaluate the functions of LINC00668 in CRC cells. Bioinformatics analyses were used to identify the LINC00668-specific binding with miRNAs that were screened by RNA pull-down. RNA immunoprecipitation and luciferase gene report assay were performed to confirm the interaction between miR-188-5p and LINC00668 in CRC cells. LINC00668 was significantly upregulated in CRC tissues and cells. Knockdown of LINC00668 suppressed cell proliferation and migration potential and induced cell apoptosis, but inhibition of miR-188-5p which was predicted to bind with LINC00668 reversed these effects. Furthermore, USP47 was a direct target of miR-188-5p, and overexpression of USP47 attenuated LINC00668 knockdown-induced tumor suppressive effects in CRC cells. Conclusively, our findings demonstrated that lncRNA LINC00668 acted as an oncogenic role in CRC cells by sponging miR-188-5p and upregulating USP47 and may represent a potential marker for CRC patients.

Asunto(s)

Carcinogénesis/genética , Progresión de la Enfermedad , MicroARNs/genética , ARN Largo no Codificante/genética , Ubiquitina Tiolesterasa/genética , Apoptosis/genética , Secuencia de Bases , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen , Humanos , Proteasas Ubiquitina-Específicas

RESUMEN

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in non-small cell lung cancer (NSCLC) progression. Recently, a newly identified lncRNA, LncRNA LINC00668 (LINC00668), was reported to be involved in the regulation of progression of several tumors. However, the expression pattern and biological function of LINC00668 in NSCLC remains largely unclear. In this study, we found that LINC00668 expression was significantly up-regulated in both NSCLC tissues and cell lines. we also showed that LINC00668 upregulation was induced by transcription factor STAT3. Clinical investigation demonstrated that high expression level of LINC00668 was associated with advanced TNM stage, histological grade and lymph node metastasis. Moreover, multivariate analysis confirmed LINC00668 expression level to be an independent prognostic indicator for overall survival of NSCLC patients. Functional assays indicated that knockdown of LINC00668 suppressed NSCLC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic studies indicated that LINC00668 is a direct target of miR-193a, leading to down-regulation in the expression of its target gene KLF7. Our findings suggested that STAT3-induced LINC00668 contributed to NSCLC progression through upregulating KLF7 expression by sponging miR-193a, and may serve as a prognostic biomarker and a potential target for NSCLC.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Factor de Transcripción STAT3/metabolismo , Regiones no Traducidas 3'/genética , Células A549 , Apoptosis/genética , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias Pulmonares/genética , Masculino , MicroARNs/genética , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Metástasis de la Neoplasia , Modelos de Riesgos Proporcionales , ARN Largo no Codificante/genética , Análisis de Regresión , Transducción de Señal , Regulación hacia Arriba/genética

RESUMEN

Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.

Asunto(s)

Carcinoma de Células Escamosas/genética , MicroARNs/genética , Neoplasias de la Boca/genética , ARN Largo no Codificante/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Congresos como Asunto , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias de la Boca/patología

RESUMEN

BACKGROUND: As most lung cancer patients present with invasive, metastatic disease, it is vital to investigate anti-metastatic treatments for non-small cell lung cancer (NSCLC). Houttuynia cordata is commonly used as a Chinese anticancer medicine in the clinic, and sodium new houttuyfonate (SNH), a main compound of this herb, has long been found to have antibiotic effects, although its anticancer effects have not been investigated. Here, we tried to address this lack of research from the perspective of the competing endogenous RNA (ceRNA) theory. METHODS: The effects of SNH on NSCLC cells were analysed with Cell Counting Kit-8 assays and colony formation assays. In addition, transwell assays and wound healing assays were used to determine the effects of SNH on migration and invasion in NSCLC cells. The levels of key genes and proteins were examined by quantitative real-time PCR, western blotting, immunofluorescence staining and IHC staining. Through transcriptome screening and digital gene expression profiling, Linc00668 was identified to be regulated by SNH. Dual-luciferase reporter assays and RNA immunoprecipitation assays verified the binding efficiency between miR-147a and Linc00668 or Slug. RESULTS: In the present study, SNH regulated NSCLC cells in multiple ways, the most prominent of which was suppressing the expression of Linc00668, which was indicated to promote migration and invasion in NSCLC cells. Functional studies demonstrated that Linc00668 acted as a ceRNA by sponging miR-147a to further regulate Slug mRNA levels, thereby influencing the progression of the epithelial-mesenchymal transition. Consistently, the results of in vivo animal models showed that SNH depressed Linc00668 and suppressed the metastasis of NSCLC. CONCLUSIONS: SNH suppressed metastasis of NSCLC cells and the mechanism may involve with the Linc00668/miR-147a/Slug axis.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , MicroARNs/genética , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Medicamentos Herbarios Chinos/farmacología , Houttuynia , Humanos , Neoplasias Pulmonares/patología , Ratones , Metástasis de la Neoplasia , Transfección

RESUMEN

Recently, long noncoding RNAs (lncRNAs) have been reported to have crucial regulatory efficiency in human cancer biology. Long intergenic non-coding RNA 668 (LINC00668) was regarded as an oncogene in multiple cancers. However, the underlying molecular mechanism of LINC00668 in oral squamous cell carcinoma (OSCC) has not been studied. In this study, we first demonstrated that LINC00668 expression was up-regulated, which was correlated with tumor progression, and miR-297 down-regulated in OSCC tissues and cells. Importantly, LINC00668 expression was negatively correlated with miR-297 expression in OSCC tissues. Loss-of-function of LINC00668 revealed that LINC00668 functioned as a ceRNA for miR-297 to facilitate VEGFA expression, promoting OSCC progression. Furthermore, LINC00668 knockdown suppressed tumor growth and reduced the expression of proliferation antigen ki-67 in vivo. Finally, we confirmed that LINC00668 promoted OSCC activity through VEGFA signaling. In conclusion, these results suggest that LINC00668 promotes OSCC tumorigenesis via miR-297/VEGFA axis, which may provide a new target for the diagnosis and therapy of OSCC disease.

Asunto(s)

Carcinoma de Células Escamosas/metabolismo , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Neoplasias de la Boca/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Humanos , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , ARN Largo no Codificante/metabolismo , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/genética

RESUMEN

Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. By utilizing publicly available lncRNAs expression profiling data and integrating analyses, we screened out LINC00668, whose expression is significantly increased and correlated with outcomes in gastric cancer (GC). Further experiments revealed that LINC00668 knockdown significantly repressed proliferation, both in vitro and in vivo. Mechanistic investigations showed that LINC00668 was a direct transcriptional target of E2F transcription factor 1 (E2F1). We further demonstrated that LINC00668 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors (CKIs), including p15, p16, p21, p27 and p57, thus contributing to the regulation of the gastric cancer cell cycle. Our results suggest that E2F1-activated LINC00668, as a cell cycle regulator, enriches the mechanistic link between lncRNA and the E2F1-mediated cell cycle regulation pathway and may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.

Asunto(s)

Proliferación Celular , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/antagonistas & inhibidores , Factor de Transcripción E2F1/metabolismo , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Neoplasias Gástricas/patología , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/genética , Factor de Transcripción E2F1/genética , Femenino , Estudios de Seguimiento , Silenciador del Gen , Humanos , Metástasis Linfática , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Tasa de Supervivencia , Células Tumorales Cultivadas , Regulación hacia Arriba , Ensayos Antitumor por Modelo de Xenoinjerto