RESUMO
Osteosarcoma is a highly aggressive cancer common in children and adolescents. There is still a lack of effective treatments for metastatic or recurrent osteosarcoma. The role of long non-coding RNAs (lncRNAs) in osteosarcoma has gradually attracted attention. Here, we identified lncRNAs that were abnormally expressed in metastatic osteosarcoma through analyzing the sequencing data of osteosarcoma tissues and selected upregulated lncRNA MELTF-AS1 for detailed study. The qRT-PCR analysis showed that the expression of MELTF-AS1 was increased in osteosarcoma tissues and cells, and the high expression of MELTF-AS1 indicated a poor prognosis of osteosarcoma patients. The high expression of MELTF-AS1 in osteosarcoma was partly due to the transcriptional activation of RREB1. The results of transwell assays, scratch wound healing assays, and the tail vein injection lung metastasis model demonstrated that knocking down MELTF-AS1 inhibited metastasis ability of osteosarcoma cells. Furthermore, the results of RNA pull-down assays, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays revealed that MELTF-AS1 could regulate MMP14 expression through interaction with miR-485-5p. Our study suggested that MELTF-AS1 functioned as a pro-metastasis gene in osteosarcoma by upregulating MMP14 and that it could be a potential therapeutic and diagnostic target for osteosarcoma.
RESUMO
Thyroid cancer is a commonly diagnosed endocrine malignancy with increasing incidence worldwide. Long noncoding RNAs (lncRNAs) are known to function in the invasion and metastasis of thyroid cancer. According to the GSE66783 microarray dataset, long intergenic nonprotein coding RNA 284 (LINC00284) is aberrantly upregulated in thyroid cancer tissues. However, information regarding the specific role of LINC00284 in thyroid cancer remains elusive. Therefore, the current study set out to determine the role of LINC00284 in the development of thyroid cancer, along with an investigation of the underlying molecular mechanism. In parallel with the microarray data from GSE66783, LINC00284 was observed to be expressed at high levels in thyroid cancer cell lines. Moreover, loss-of-function experiments revealed that the downregulation of LINC00284 reduced aldehyde dehydrogenase (ALDH) activity and thyroid cancer cell proliferation, colony formation, and invasiveness, which promoted cell apoptosis. Mechanistically, using dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays, LINC00284 was identified to competitively bind to microRNA-30d-5p (miR-30d-5p), which was observed to be expressed at low levels in thyroid cancer tissues and cells and directly targets the oncogene a disintegrin and metalloproteinase 12 (ADAM12). Overexpression of miR-30d-5p exerted tumor-suppressive effects on the malignant activity of thyroid cancer cells, changes that were reversed by LINC00284 overexpression or ADAM12 overexpression. Furthermore, LINC00284 activated the Notch signaling pathway by competitively binding to miR-30d-5p and increasing the expression of ADAM12. Finally, by performing in vivo experiments, we found that LINC00284 silencing or miR-30d-5p overexpression suppressed the tumorigenic ability of thyroid cancer cells and that overexpression of miR-30d-5p inhibited the LINC00284-induced tumorigenesis of thyroid cancer cells. Collectively, our findings indicate that LINC00284 competitively binds to miR-30d-5p and activates the ADAM12-dependent Notch signaling pathway, thereby promoting the development of thyroid cancer.
RESUMO
OBJECTIVE: Alzheimer's disease (AD) is considered a neurodegenerative disease that affects the cognitive function of elderly individuals. In this study, we aimed to analyze the neuroprotective potential of isoquercetin against the in vitro and in vivo models of AD and investigated the possible underlying mechanisms. MATERIALS AND METHODS: The experimental study was performed on PC12 cells treated with lipopolysaccharide (LPS). Reactive oxygen species (ROS), antioxidant parameters, and pro-inflammatory cytokines were measured. In an in vivo approach, Wistar rats were used and divided into different groups. We carried out the Morris water test to determine the cognitive function. Biochemical parameters, antioxidant parameters, and pro-inflammatory parameters were examined. RESULTS: The non-toxic effect on PC12 cells was shown by isoquercetin. Isoquercetin significantly reduced the production of nitrate and ROS, along with the altered levels of antioxidants. Isoquercetin significantly (P<0.001) down-regulated proinflammatory cytokines in PC12 cells treated with LPS. In the in vivo approach, isoquercetintreated groups considerably showed the up-regulation in the latency and transfer latency time, as compared with AD groups. Isoquercetin significantly reduced Aß-peptide, protein carbonyl, while enhanced the production of brainderived neurotrophic factor (BDNF) and acetylcholinesterase (AChE). Isoquercetin significantly (P<0.001) reduced pro-inflammatory cytokines and inflammatory mediators, as compared with AD groups. CONCLUSION: Based on the results, we may infer that, through antioxidant and anti-inflammatory systems, isoquercetin prevented neurochemical and neurobehavioral modifications against the model of colchicine-induced AD rats.
