RESUMEN
The most frequent primary brain tumor in adults is glioma, yet no effective curative treatments are currently available. Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treatment. In this study, miR-155 is predicted to target JARID2. miR-155 is overexpressed in clinical glioma specimens and cell lines. miR-155 overexpression in glioma cells enhances cell viability and represses cell apoptosis. Through targeting, miR-155 inhibits JARID2 expression. miR-155 inhibition inhibits glioma cell viability and enhances cell apoptosis, whereas JARID2 knockdown enhances cell viability and inhibits cell apoptosis; JARID2 knockdown partially reverses miR-155 inhibition effects on glioma phenotypes. miR-155 inhibition reduces but knockdown of JARID2 promotes the tumor formation ability of glioma cells in vivo. Valproic acid (VPA) upregulates JARID2 expression, inhibits glioma cell viability and enhances cell apoptosis. VPA downregulates the expression level of miR-155 by increasing the methylation level of the miR-155 promoter, suggesting that the miR-155/JARID2 axis is implicated in VPA inhibition of glioma cell viability and enhancement of glioma cell apoptosis. This study demonstrates a new mechanism of VPA treatment of gliomas by affecting the miR-155/JARID2 axis, which could be regarded as a new strategy for the prevention and treatment of glioma.
Asunto(s)
Neoplasias Encefálicas , Glioma , MicroARNs , Humanos , Ácido Valproico/farmacología , Línea Celular Tumoral , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/metabolismo , MicroARNs/metabolismo , Metilación , Proliferación Celular/genética , Apoptosis/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Regulación Neoplásica de la Expresión GénicaRESUMEN
Background: Crohn's disease (CD) is a multifactorial inflammatory bowel disease characterized by complex aberrant autoimmune disorders. Currently, the involvement of the circadian rhythm in the pathogenesis of CD is unknown. Methods: Bulk and single-cell RNA-seq data and associated clinical data from patients with CD were downloaded from the Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis was performed to calculate the enrichment score (ES) of circadian rhythm-related genes. Differential expression analysis was used to identify differentially expressed genes. Functional enrichment analysis was used to explore potential disease mechanisms. CIBERSORT was used to estimate immune cell abundance. Single-cell RNA-seq data were analyzed using the R package "Seurat." Results: The ES of circadian rhythm-related genes was lower in the CD tissue than in the normal tissue. Ubiquitin-specific protease 2 (USP2), a circadian rhythm-related gene, was identified as a potential modulator of CD pathogenesis. USP2 expression was reduced in CD and was associated with disease severity. Moreover, the analysis of bulk RNA-seq and single-cell RNA-seq data showed that monocyte and neutrophil abundance was elevated in CD and was negatively correlated with USP2 expression. It should be noted that USP2 expression in acinar cells was negatively correlated with monocyte and neutrophil abundance. Functional enrichment analysis revealed several canonical pathways to be enriched in CD, including the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, cytokine-cytokine receptor interaction, toll-like receptor signaling pathway, and nod-like receptor signaling pathway. Conclusion: Aberrant expression of circadian rhythm-related genes is correlated with CD pathogenesis. USP2 might be related to crosstalk among the different cell types in CD. These findings provide insights into future chronotherapy for CD.
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Background: Long non-coding RNA LINC01232 plays an important role in the progression of metastasis in several cancers. However, the function of LINC01232 in gastric cancer is limited. Authors aimed to investigate the role and mechanism of LINC01232 in the metastasis of gastric cancer. Methods: The expression levels and correlation of LINC01232, miR-506-5p, and PAK1 were analyzed by GEPIA or ENCORI, and the abundance of LINC01232 and miR-506-5p was measured in tissues and cells via qRT-PCR, the location of LINC01232 in gastric cells was analyzed by nuclear and cytoplasmic fractionation, while the protein levels of PAK1, E-cadherin and vimentin were additionally quantified by Western blotting. Interactions between LINC01232, miR-506-5p, and PAK1 were detected through luciferase reporter assays, qRT-PCR and Western blotting. Cellular viability was evaluated through CCK8 assays, migration ability was measured by transwell assays, invasion ability was tested by wound healing experiment. Results: LINC01232 was overexpressed in gastric cancer tissues and cells, and mainly located in nucleus. The inhibition of LINC01232 could suppress migration, invasion and EMT of gastric cancer cells. MiR-506-5p was downregulated in gastric cancer tissues and cells. LINC01232 sponged miR-506-5p to accelerate migration and EMT. PAK1 was certified to be a target of miR-506-5p, inhibition of PAK1 could interrupt LINC01232 overexpression-induced migration of gastric cancer cells. Conclusion: The LINC01232/miR-506-5p/PAK1 axis promotes metastasis of gastric cancer cells.
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Picric acid (PA) is an important chemical product which has been widely used in dye manufacturing, antiseptics, and pharmaceuticals. Owing to PA's extreme electron-deficient structure, its natural degradation is hard, leading to accumulation in the environment and finally threatening the ecosystem and human health. In this case, PA detection and removal becomes more and more important, concerning environmental protection and human health. In this study, an ionic covalent organic framework (I-COF) was synthesized and modified with a luminescent Tb(III) emitter (Tb(DPA)3 3-, DPA = pyridine-2,6-dicarboxylic acid), via ionic exchange. The resulting composite material (Tb-COF) was fully characterized by geometric analysis, IR, XRD, porosity analysis, SEM/TEM, and elemental analysis. It was found that Tb(DPA)3 3- was loaded into the hexagonal cage in an I-COF host with an ionic exchange ratio of 41%. The as-synthesized Tb-COF showed weak Tb(III) emission and strong red COF emission, after adding PA, Tb(III) emission was increased whereas COF emission weakened greatly, showing sensing behavior. Linear working curves were observed with good selectivity. The sensing mechanism was revealed as follows. PA molecules replaced the [Tb(PDA)3]3- component trapped in Tb-COF, releasing free luminescent [Tb(PDA)3]3-. After incorporating PA in the hexagonal cage, the COF emission was quenched. This sensing mechanism ensured a good selectivity over competing species, including cations, anions, and nitrocompounds. The adsorption and removal performance of I-COF for PA were investigated as well.
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Ferrum (Fe) is a widely existing metal element and nearly the most important trace element in living species, including human beings. The design of chemosensors for Fe ions faces issues related to the d-d transition of Fe(II) and Fe(III) ions, which makes them efficient electron trappers and energy quenchers. Most fluorescent dyes cannot afford such d-d quenching, showing emission turn off effect towards both Fe(II) and Fe(III) ions with poor selectivity. As a consequence, the development for Fe with emission turn on effect and good selectivity shall be continued and updated. In this work, three rhodamine-derived chemosensors modified by different lengths of alkyl chains having electron-donating N and O atoms were synthesized and explored for the selective optical sensing of Fe(III). These chemosensors showed colorimetric and fluorescent emission turn on sensing for Fe(III), showing two sensing channels. These chemosensors showed good selectivity, which was assigned to the sieving effect of alkyl chains with electron-donating N and O atoms. The N atom was found to be more effective in associating with Fe(III), compared to the O atom. Their fluorescent cell imaging experiment was carried out to confirm the possibility of being used for cell imaging.
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A maximal surgical resection followed by radiotherapy and chemotherapy with temozolomide (TMZ) as the representative agent is the standard therapy for gliomas. However, tumor cell resistance to radiotherapy and chemotherapy leads to poor prognosis and high mortality in patients with glioma. In the present study, we demonstrated that JARID2 was downregulated and CCND1 was upregulated within glioma tissues of different grades and glioma cells. In tissue samples, JARID2 was negatively correlated with CCND1. JARID2 overexpression significantly inhibited glioma cell viability, promoted glioma cell apoptosis upon TMZ treatment, and increased p21, cleaved-PARP, and cleaved-caspase3 in TMZ-treated glioma cells. JASPAR tool predicted the possible binding sites between JARID2 and CCND1 promoter regions; through direct binding to CCND1 promoter region, JARID2 negatively regulated CCND1 expression. Under TMZ treatment, JARID2 overexpression inhibited CCND1 expression, promoted glioma cell apoptosis, and increased p21, cleaved-PARP, and cleaved-caspase3 in glioma cells treated with TMZ; meanwhile, CCND1 overexpression exerted opposite effects on glioma cells treated with TMZ and partially reversed the effects of JARID2 overexpression. In conclusion, JARID2 targets and inhibits CCND1. The JARID2/CCND1 axis modulates glioma cell growth and glioma cell sensitivity to TMZ.