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BACKGROUND: Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved. METHODS: Through mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo. RESULTS: We identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain-derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence. CONCLUSION: Overall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.
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OBJECTIVE: Neuroblastoma (NBL) is an extra-cranial solid tumor in children. This study was attempted to investigate the regulatory mechanism of long noncoding RNA LINC01410 (LINC01410) on NBL. METHODS: The expression of LINC01410, miR-506-3p, and WEE1 in NBL was evaluated by quantitative real time polymerase chain reaction. The proliferation and colony formation ability of NBL cells were analyzed by MTT and colony formation assay. Flow cytometry assay was executed to measure the apoptosis and cell cycle. Dual-luciferase reporter assay was used to detect the targeted relationships among LINC01410, miR-506-3p, and WEE1. Additionally, the role of LINC01410 on NBL in vivo was evaluated according to a tumor xenograft model. RESULTS: The expression of LINC01410 and WEE1 was enhanced and miR-506-3p was inhibited in NBL. LINC01410 knockdown attenuated the cell proliferation, colony formation ability, and inhibited tumor growth. Moreover, LINC01410 silencing facilitated the apoptosis and arrested the cell cycle. LINC01410 interacted with miR-506-3p to elevate the WEE1 expression in NBL. Additionally, miR-506-3p inhibition or WEE1 overexpression weakened the reduction effects of sh-LINC01410 on cell proliferation, colony formation ability, apoptosis, and cell cycle. CONCLUSIONS: Knockdown of LINC01410 inhibited the development of NBL by miR-506-3p/WEE1 axis in vitro, which could serve as a potential therapeutic target for NBL therapy.
Assuntos
Carcinogênese/genética , Proteínas de Ciclo Celular/genética , MicroRNAs/genética , Neuroblastoma/genética , Proteínas Tirosina Quinases/genética , RNA Longo não Codificante/metabolismo , Animais , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Lactente , Masculino , Camundongos , MicroRNAs/metabolismo , Transplante de Neoplasias , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Proteínas Tirosina Quinases/metabolismo , RNA Longo não Codificante/genética , Carga Tumoral/genética , Ensaio Tumoral de Célula-TroncoRESUMO
Ganoderma lucidum is an edible medicinal mushroom known as "Lingzhi" in China and "Reishi or Manetake" in Japan. It is a highly prized vitality-enhancing herb for >2000 years. G. lucidum polysaccharide (GLPS) has been identified as one of the major bioactive components and developed into a drug named "Ji 731 Injection" in China since 1973. The large-scale production of the drug began in 1985 and approved by the Chinese FDA as "Polysacharidum of G. lucidum Karst Injection in 2000, which is applied intramuscularly. After more than 40 years of clinical use, its efficacy, safety, and long-term tolerability have been recognized by neurologists. It is one of a few non-hormonal drugs used for treating neurosis, polymyositis, dermatomyositis, atrophic myotonia and muscular dystrophy. It is also used for combination therapy, which reduces the amount of glucocorticoid required for myopathy patient who is in remission. In addition, it reduces adverse reactions and improves the quality of life for cancer patients during chemotherapy. We found 81 qualified chemical, biochemical, preclinical, and clinical studies of GLPS both in English and Chinese spanning from 1973 to 2017 by searching CNKI (China National Knowledge Infrastructure), Wan Fang, and PubMed databases. The molecular mechanisms underlying GLPS's antioxidant, anti-tumor, immune-modulatory, hypoglycemic, hypolipidemic, and other activities are discussed. Both preclinical and clinical studies are either deliberated or indexed in current article. We aimed to provide a molecular picture as well as a clinical basis to comprehend GLPS as one of few polysaccharide-based modern medicines with complicated chemical and pharmacological properties.