ABSTRACT
PURPOSE: Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, which has high metastasis. MicroRNAs (miRNAs) have been reported to participate in RCC progression. The present study aimed to understand the biological role and mechanism of miR-378a-3p in RCC. METHODS: RT-qPCR assay was used to assess miR-378a-3p and transducer of ERBB2 (TOB2) expression in RCC tissues and cell lines. CCK-8, clone formation, scratch, and transwell assays were carried out to evaluate cell proliferation, migration, and invasion. Furthermore, the target genes of miR-378a-3p were predicted by the online bioinformatics databases. Dual-luciferase reporter assay was used to validate the relationship between miR-378a-3p and TOB2. RESULTS: miR-378a-3p was highly expressed in RCC tissues and RCC cell lines. Besides, miR-378a-3p accelerated the progression of RCC by mediating cell proliferation, migration and invasion. More importantly, TOB2 was confirmed as a potential target gene of miR-378a-3p. The results of loss-of-function experiments showed that inhibition of TOB2 reversed the inhibitory roles of miR-378a-3p inhibitor on RCC progression. CONCLUSIONS: miR-378a-3p promoted cell proliferation, migration and invasion through regulating TOB2 in RCC, which indicated a promising target for the treatment of RCC.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , MicroRNAs , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , MicroRNAs/metabolism , Cell Line , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Cell Proliferation , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell MovementABSTRACT
The development of sustainable routes for the synthesis of metal organic frameworks (MOFs) is very important because of the wide applications of MOFs on a large scale in the fields of adsorption, separation, and catalysis. ZIF-8, a zinc-based zeolitic imidazolate framework (ZIF), was first prepared following a solvent-free method from zinc acetate and denoted as ZIF-8-DGUT. The synthesis was conducted with the addition of an appropriate amount of sodium hydroxide (NaOH) powder before fully grinding, and the synthesis was accomplished at mild temperature at 343 K for 24 h. This strategy provided a practical method for the production of ZIF materials.
ABSTRACT
BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore, it is an important goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.
Subject(s)
Gene Expression Regulation, Neoplastic/genetics , Hepatocytes/metabolism , Hepcidins/genetics , SOXB1 Transcription Factors/genetics , Anemia/genetics , Anemia/metabolism , Binding Sites , Bone Morphogenetic Protein 2/metabolism , Gene Knockdown Techniques , Genetic Vectors , Hep G2 Cells , Hepcidins/metabolism , Humans , Interleukin-6/metabolism , Iron/metabolism , Luciferases , Plasmids/genetics , Promoter Regions, Genetic/genetics , SOXB1 Transcription Factors/metabolismABSTRACT
BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore,itis animportant goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.