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1.
J Bioenerg Biomembr ; 52(1): 17-25, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31927658

RESUMO

Dysregulation of cerebral microvascular endothelial cells plays an important role in the pathogenesis of stroke. However, the underlying mechanisms still need to be elucidated. In the current study, we found that the long non-coding RNA (lncRNA) FAL1 was significantly reduced in response to oxygen-glucose deprivation and reoxygenation (OGD/R) stimulation in human primary brain microvascular endothelial cells (HBMVECs). Interestingly, overexpression of FAL1 ameliorated OGD/R-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and increasing the level of reduced glutathione (GSH). Also, overexpression of FAL1 suppressed OGD/R-induced secretions of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and high mobility group box-1 (HMGB-1). We then found that OGD/R-induced reduction of cell viability and release of lactate dehydrogenase (LDH) were prevented by overexpression of FAL1. Additionally, exposure to OGD/R significantly reduced the phosphorylated levels of PAK1 and AKT as well as the total level of proliferating cell nuclear antigen (PCNA), which was restored by overexpression of FAL1. Importantly, overexpression of FAL1 restored OGD/R-induced reduction in the expression of endothelial nitric oxide synthase (eNOS) and the subsequent release of nitric oxide (NO). Our results implicate that FAL1 might be involved in the process of brain endothelial cell damage.


Assuntos
Encéfalo/fisiopatologia , Células Endoteliais/metabolismo , RNA Longo não Codificante/metabolismo , Quinases Ativadas por p21/metabolismo , Hipóxia Celular , Humanos , Transdução de Sinais
2.
J Cell Biochem ; 120(7): 11471-11477, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30746742

RESUMO

Genetic studies on cancers have revealed that lncRNA-GAS5 and lncRNA-FAL1 are overexpressed in some cancerous cells. The aim of the present investigation was to evaluate the roles of lncRNA-GAS5 and lncRNA-FAL1 gene expression changes in the diagnosis and prognosis of patients with papillary thyroid carcinoma (PTC). In a case-control investigation, we recruited a total of 140 formalin-fixed paraffin-embedded tissues of PTC, including 70 cancerous and noncancerous tissues. Quantitative real-time polymerase chain reaction was used to determine the lncRNA-GAS5 and lncRNA-FAL1 level of gene expression in the two tissue groups. The association between the clinicopathological characteristics of patients and the expression level of lncRNA-GAS5 and lncRNA-FAL1 was evaluated. Our findings revealed that the level of expression in the lncRNA-GAS5 and lncRNA-FAL1 genes was significantly upregulated in thyroid cancerous tissues (P < 0.003 and P < 0.040, respectively). The expression of lncRNA-GAS5 and lncRNA-FAL1 revealed a significant association with tumor node metastasis staging (P < 0.042 and P < 0.001, respectively). It seems that the lncRNA-GAS5 and lncRNA-FAL1 genes play an oncogenic role in PTC. The two genes have a significant potential prognostic value and may likely be used as novel therapeutic targets for PTC patients in the future.

3.
IUBMB Life ; 70(11): 1093-1100, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30290064

RESUMO

Aberrant expression of long non-coding RNAs (lncRNAs) has been associated with a variety of malignancies including colon cancer. In this study, we aimed to characterize the biological mechanisms of focally amplified lncRNA on chromosome 1 (FAL1) in colon cancers. Here, our results indicate that FAL1 expression was remarkably up-regulated in colon tumor tissues as compared to corresponding tumor-adjacent normal tissues. Importantly, the cumulative survival rate of patients with high levels of FAL1 in tumor tissues was considerably lower than those with low FAL1 levels in tumor tissues. Cox regression analysis showed that lncRNA FAL1 could act as an independent prognostic factor in CRC. Knockdown of FAL1 in HT29 cells attenuated cell proliferation and stimulated cell apoptosis. In contrast, overmetastasis-related molecules Bcl-2, TGF-ß1, p65, and PCNA at the mRNA and protein levels. Mechanistically, FAL1 was found to interact with STAT3 at 200 to 400 bp and promote phosphorylation of STAT3. In addition, we found that knockdown of STAT3 in HT29 cells abolished the effects of FAL1 on cell proliferation as well as the expression of TGF-ß1 and Bcl-2. Based on these findings, we concluded that FAL1 might be a potential oncogene for the progression of colon cancer. © 2018 IUBMB Life, 70(11):1093-1100, 2018.


Assuntos
Apoptose , Proliferação de Células , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Movimento Celular , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Humanos , Prognóstico , Transdução de Sinais , Taxa de Sobrevida , Células Tumorais Cultivadas
4.
Cell Physiol Biochem ; 43(1): 339-352, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28854421

RESUMO

BACKGROUND/AIMS: Recently, long non-coding RNAs (lncRNAs) have been found to have many biological effects in different cancer stages. Several studies have revealed that focally amplified lncRNA on chromosome 1 (FAL1) regulates cancer progression via p21. However, the expression and mechanism of FAL1 in non-small cell lung cancer (NSCLC) still remain unclear. METHODS: We detected the FAL1 level in NSCLC tissues and in established cell lines using quantitative real-time PCR and evaluated the clinical significance. FAL1 was silenced or overexpressed using siRNA or lentivirus to study whether FAL1 affected cell proliferation, invasion and migration. Xenograft growth and pulmonary metastasis were observed using nude mouse models. The mechanisms were explored with western blotting and immunohistochemistry. RESULTS: FAL1 was significantly overexpressed in NSCLC compared with adjacent normal tissues, and a high level of FAL1 correlated with poor histological grade, increased lymph node metastasis and advanced TNM stage. Loss- and gain-of-function experiments in vitro verified that knockdown of FAL1 inhibited cell proliferation, invasion, migration and EMT via the PTEN/AKT pathway. Furthermore, an in vivo assay confirmed that overexpression of FAL1 facilitated tumor growth and metastasis. CONCLUSION: FAL1 may promote tumorigenesis and progression of NSCLC through the PTEN/AKT axis, which could lead to lncRNA-related diagnostics and therapeutics in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Pulmonares/patologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Idoso , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Proteína Quinase 7 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 7 Ativada por Mitógeno/genética , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/genética , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , Transdução de Sinais
5.
J Physiol Biochem ; 79(3): 669-682, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37147492

RESUMO

Current evidence finds that circulating exosomal lncRNA focally amplified lncRNA on chromosome 1 (FAL1) promotes the progression of hepatocellular carcinoma (HCC). However, the underlying mechanism of serum extracellular vesicular FAL1 in HCC progression remains elusive. Here, we extracted extracellular vesicles (EVs) from serum samples of HCC patients and healthy volunteers, and found that FAL1 was highly enriched in the serum EVs of HCC patients. Then, macrophages were treated with EVs alone or together with small interfering RNA against FAL1 (si-FAL1). The data indicated that FAL1-enriched EVs induced macrophage M2 polarization, while silencing FAL1 in macrophages antagonized the role of EVs. Moreover, HepG2 cells were co-cultured with the conditioned macrophages, and co-culturing with EVs-incubated macrophages promoted HepG2 cell proliferation, invasion, cell cycle progression, and colony formation, and inhibited cell apoptosis and sorafenib sensitivity, while interfering FAL1 in macrophages reversed these effects. Consistently, ectopic expression of FAL1 in macrophages also induced macrophage M2 polarization, and co-culture of FAL1-overexpressing macrophages with HepG2 cells facilitated the malignant progression of HepG2 cells. Furthermore, co-culturing HepG2 cells with EVs-incubated macrophages activated the Wnt/ß-catenin signaling pathway, and treatment with a Wnt/ß-catenin pathway inhibitor IWP-2 partially neutralized the effect of EVs-incubated macrophages on HepG2 cell malignant behaviors. Additionally, FAL1 enriched EVs-incubated macrophages markedly increased mouse xenograft tumor growth. In conclusion, extracellular vesicular lncRNA FAL1 promotes macrophage M2 polarization and further activates the Wnt/ß-catenin signaling pathway in HCC cells, thus promoting HCC progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ativação de Macrófagos , RNA Longo não Codificante , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proliferação de Células , Vesículas Extracelulares , Humanos , Células Hep G2 , Via de Sinalização Wnt , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Animais , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais
6.
Cancers (Basel) ; 13(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203279

RESUMO

We investigated the regulatory mechanism of FAL1 and unravelled the molecular biological features of FAL1 upregulation in papillary thyroid cancer (PTC). Correlation analyses of FAL1 and neighbouring genes adjacent to chromosome 1q21.3 were performed. Focal amplification was performed using data from copy number alterations in The Cancer Genome Atlas (TCGA) database. To identify putative transcriptional factors, PROMO and the Encyclopaedia of DNA Elements (ENCODE) were used. To validate c-JUN and JUND as master transcription factors for FAL1 and ECM1, gene set enrichment analysis was performed according to FAL1 and ECM1 expression. Statistical analyses of the molecular biological features of FAL1- and ECM1-upregulated PTCs were conducted. FAL1 expression significantly correlated with that of neighbouring genes. Focal amplification of chromosome 1q21.3 was observed in ovarian cancer but not in thyroid carcinoma. However, PROMO suggested 53 transcription factors as putative common transcriptional factors for FAL1 and ECM1 simultaneously. Among them, we selected c-JUN and JUND as the best candidates based on ENCODE results. The expression of target genes of JUND simultaneously increased in FAL1- and ECM1-upregulated PTCs, especially in young patients. The molecular biological features represented RAS-driven PTC and simultaneously enriched immune-related gene sets. FAL1 and ECM1 expression frequently increased simultaneously and could be operated by JUND. The simultaneous upregulation might be a potential diagnostic and therapeutic target for RAS-driven PTC.

7.
Biomed Pharmacother ; 118: 109212, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31387003

RESUMO

Focally amplified lncRNA on chromosome 1 (FALEC) is novel lncRNA located in a focal amplicon on chromosome 1q21.2, and has been identified as an oncogenic properties in a variety of human cancers. However, there was no report about the expression pattern and biological function of FALEC in endometrial cancer. In our research, FALEC expression was increased in endometrial cancer tissue samples and cell lines compared with corresponding paracancerous normal tissue samples and cell line, respectively. Furthermore, we investigated the clinical significance of FALEC in endometrial cancer patients, and found endometrial cancer patients with advanced clinical stage or large tumor size had higher levels of FALEC expression than those with early clinical stage or small tumor size. The in vitro studies showed silencing of FALEC expression inhibited cell proliferation and arrested cell cycle at G0/G1. In conclusion, FALEC is overexpressed in endometrial cancer tissues and cells, and involved in regulating cell proliferation and cell-cycle.


Assuntos
Carcinogênese/genética , Ciclo Celular/genética , Proliferação de Células/genética , Neoplasias do Endométrio/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias do Endométrio/patologia , Feminino , Inativação Gênica , Humanos , Estadiamento de Neoplasias , RNA Interferente Pequeno/genética , Regulação para Cima
8.
Life Sci ; 236: 116918, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610208

RESUMO

Long noncoding RNAs (lncRNAs) are characterized as a group of endogenous RNAs that are more than 200 nucleotides in length and have no protein-encoding function. More and more evidence indicates that lncRNAs play vital roles in various human diseases, especially in tumorigenesis. Focally amplified lncRNA on chromosome 1 (FAL1), a novel lncRNA with enhancer-like activity, has been identified as an oncogene in multiple cancers and high expression level of FAL1 is usually associated with poor prognosis. Dysregulation of FAL1 has been shown to promote the proliferation and metastasis of cancer cells. In the present review, we summarized and illustrated the functions and underlying molecular mechanisms of FAL1 in the occurrence and development of different cancers and other diseases. FAL1 has the potential to appear as a feasible diagnostic and prognostic tool and new therapeutic target for cancer patients though further investigation is needed so as to accelerate clinical application.


Assuntos
Carcinogênese/genética , Carcinogênese/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Neoplasias/patologia , RNA Longo não Codificante/genética , Humanos , Transdução de Sinais
9.
Int J Biochem Cell Biol ; 106: 46-56, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30267804

RESUMO

LncRNA FAL1 has been demonstrated to play an important role in promoting carcinogenesis via the ceRNA mechanism in several types of cancer. However, the role and the mechanism of lncRNA FAL1 in CRC remain unclear. Here our results demonstrate that lncRNA FAL1 is markedly upregulated in CRC tissues and cells, and lncRNA FAL1 promotes proliferation ability, migration and invasion in CRC cells. Additionally, we demonstrate that lncRNA FAL1 acts as a sponge of miR-637, which functions as a suppressor via targeting and downregulation of NUPR1 expression. Moreover, we demonstrate that lncRNA FAL1 promotes carcinogenesis of CRC cells via regulation of the miR-637/NUPR1 pathway. Taken together, our findings underscore the crucial roles of lncRNA FAL1 in CRC carcinogenesis and its potential prognostic and therapeutic value.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Movimento Celular , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Transdução de Sinais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Colorretais , Células HCT116 , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética
10.
Artif Cells Nanomed Biotechnol ; 47(1): 896-903, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30873881

RESUMO

Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of a variety of malignancies, including oesophageal cancer. Alterations of the lncRNA focally amplified lncRNA on chromosome 1 (FAL1) are present in epithelial tumours. However, its expression pattern and function in oesophageal cancer are poorly addressed. In the current study, we reported that FAL1 is upregulated in oesophageal cancer tissues and is positively correlated with outcomes in oesophageal squamous cell carcinoma (OSCC). Consecutive experiments revealed that the expression level of FAL1 is higher in OSCC cell lines than in human normal oesophageal epithelium cell line HEEpiCs. Importantly, Knockdown of FAL1 suppressed cell proliferation, increased cell cycle arrest, inhibited cell invasion and epithelial-mesenchymal transition (EMT) by affected related genes. In contrast, overexpression of FAL1 has the opposite effects. Our findings underline a novel biological mechanism in which FAL1 acts as a regulator of oesophageal cancer cells and may provide insights into novel therapeutic strategies for oesophageal cancer.


Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Longo não Codificante/fisiologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/genética , Invasividade Neoplásica/genética , Prognóstico , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética
11.
Life Sci ; 197: 122-129, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29421439

RESUMO

BACKGROUND: Long non-coding RNAs (LncRNAs) have been demonstrated to play crucial role in tumor growth and metastasis for hepatocellular carcinoma (HCC). LncRNA FAL1 has been indicated to promote the progression of various cancers. However, the role of lncRNA FAL1 in HCC was poorly understood. METHODS: The expression levels of lncRNA FAL1 in HCC tissues and cells were determined by RT-qPCR. The roles of lncRNA FAL1 on HCC cells were investigated by MTT, colony formation, transwell, RT-qPCR, and Western blotting. The miRNA binding sites of lncRNA FAL1 was predicted using RegRNA 2.0 and miR-1236 was validated to target lncRNA FAL1 by luciferase reporter assays and RT-qPCR. Finally, the expression levels of lncRNA FAL1 in serum exosome of HCC patients was also investigated and the role of exosome-mediated lncRNA FAL1 was further investigated by co-culturing with HCC cells. RESULTS: This study first showed that lncRNA FAL1 was up-regulated in HCC tissues and functioned as an oncogene in HCC. LncRNA FAL1 could accelerate cell proliferation and metastasis as a ceRNA mechanism by competitively binding to miR-1236. Moreover, lncRNA FAL1 was also up-regulated in serum exosome of HCC patients and could transfer lncRNA FAL1 to HCC cells to increase their abilities of cell proliferation and migration. CONCLUSIONS: Taken together, this study indicated that lncRNA FAL1 functions as an oncogenic in HCC and may be a novel diagnostic biomarker or a novel target for the treatment of HCC in future.


Assuntos
Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Regulação para Cima , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética
12.
Artigo em Chinês | WPRIM | ID: wpr-988373

RESUMO

Objective To observe the expression difference of lncRNA FAL1 in ovarian cancer cells and their drug-resistant cell lines, and to explore the effect and mechanism of lncRNA FAL1 down-regulation on cell chemotherapy resistance. Methods The expression levels of fal1 gene in SKOV3 and COC1 cells and their drug-resistant cell lines were detected by qRT-PCR. fal1 siRNA was transfected to downregulate fal1 gene expression. MTT was used to detect cell proliferation. Transwell method was used to detect cell invasion ability. Plate clone formation test was used to detect cell clone ability, and Western blot was used to detect MDR-1, mpr-1, ABCG2 and phosphorylation levels of p38 MAPK, ERK1/2 and JNK. SKOV3/DDP and COC1/DDP cells transfected with FAL1-siRNA were injected subcutaneously into BALB/c nude mice. The volume and mass of subcutaneous transplanted tumors were measured. Results Compared with SKOV3 and COC1 cells, SKOV3/DDP and COC1/DDP cells were less sensitive to DDP, and the expression levels of FAL1 gene increased (P < 0.01). After transfection with FAL1-siRNA, the sensitivity of SKOV3/DDP and COC1/DDP cells to DDP increased (P < 0.01), and the invasion (P < 0.05) and cloning ability (P < 0.01) decreased. The expression levels of MDR-1, MPR-1, ABCG2 (P < 0.01) and the phosphorylation levels of p38 MAPK, ERK1/2 and JNK (P < 0.05) decreased. The volume and mass of subcutaneous transplanted tumors were significantly reduced (P < 0.01). Conclusion Down-regulation of lncRNA FAL1 could significantly reduce the chemotherapy resistance of cisplatin-resistant ovarian cancer cell lines and inhibit the proliferation of drug-resistant cells in vivo. Its mechanism is related to inhibiting the activation of MAPK signaling pathway.

13.
J. physiol. biochem ; 79(3): 669-682, ago. 2023.
Artigo em Inglês | IBECS (Espanha) | ID: ibc-223756

RESUMO

Current evidence finds that circulating exosomal lncRNA focally amplified lncRNA on chromosome 1 (FAL1) promotes the progression of hepatocellular carcinoma (HCC). However, the underlying mechanism of serum extracellular vesicular FAL1 in HCC progression remains elusive. Here, we extracted extracellular vesicles (EVs) from serum samples of HCC patients and healthy volunteers, and found that FAL1 was highly enriched in the serum EVs of HCC patients. Then, macrophages were treated with EVs alone or together with small interfering RNA against FAL1 (si-FAL1). The data indicated that FAL1-enriched EVs induced macrophage M2 polarization, while silencing FAL1 in macrophages antagonized the role of EVs. Moreover, HepG2 cells were co-cultured with the conditioned macrophages, and co-culturing with EVs-incubated macrophages promoted HepG2 cell proliferation, invasion, cell cycle progression, and colony formation, and inhibited cell apoptosis and sorafenib sensitivity, while interfering FAL1 in macrophages reversed these effects. Consistently, ectopic expression of FAL1 in macrophages also induced macrophage M2 polarization, and co-culture of FAL1-overexpressing macrophages with HepG2 cells facilitated the malignant progression of HepG2 cells. Furthermore, co-culturing HepG2 cells with EVs-incubated macrophages activated the Wnt/β-catenin signaling pathway, and treatment with a Wnt/β-catenin pathway inhibitor IWP-2 partially neutralized the effect of EVs-incubated macrophages on HepG2 cell malignant behaviors. Additionally, FAL1 enriched EVs-incubated macrophages markedly increased mouse xenograft tumor growth. In conclusion, extracellular vesicular lncRNA FAL1 promotes macrophage M2 polarization and further activates the Wnt/β-catenin signaling pathway in HCC cells, thus promoting HCC progression. (AU)


Assuntos
Humanos , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Macrófagos/metabolismo , Proliferação de Células , Linhagem Celular Tumoral
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