ABSTRACT
Background: Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive tumor of non-Hodgkin's lymphoma. The role of micro ribonucleic acid (RNA) (miR)-363 in NKTCL has not yet been elucidated. The present study aimed to investigate the potential role of miR-363 in NKTCL. Methods: The expression of the top five differentially expressed microRNAs (miRNAs) as well as sirtuin 6 (SIRT6) in NK normal cells and its tumor cell lines were explored. The clinical tissues of NKTCL patients were collected and analyzed for expression of miR-363 and SIRT6. In addition, human NK/T-cell lymphoma cells (SNK-6) were transfected into different groups to detect cell proliferation and apoptosis abilities through cell counting kit 8 (CCK-8) experiment and flow cytometry analysis. Western blot assay was employed to examine protein expression. NKTCL nude mice models were constructed by subcutaneous injection of stably transfected SNK-6 cells to validate the mechanism of miR-363 in NKTCL via SIRT6 in vivo. Results: MiR-363 was down-regulated in NKTCL tissues and cell lines. Overexpression of miR-363 inhibited cell proliferation and promoted cell apoptosis. In contrast, SIRT6 was up-regulated in NKTCL and proved to be a downstream target of miR-363. SIRT6 could activate the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Also, miR-363 mimic could suppress the proliferation and induce the apoptosis of NKTCL via the SIRT6/PI3K/AKT axis both in vitro and in vivo. Conclusions: MiR-363 suppresses the SIRT6/PI3K/AKT pathway to restrain cell proliferation and accelerate cell apoptosis during NKTCL progression.
ABSTRACT
BACKGROUND: This study aims to explore the relationship between serum vitamin A and 25-hydroxyvitamin D3 (25OHD3) levels with pulmonary function and quality of life (QOL) in children with stable asthma. METHODS: A total of 117 cases of children with stable asthma were assigned into the case group and 129 healthy children underwent physical examination during the same period into the control group. Electrochemiluminescence was employed to determine serum vitamin A and 25OHD3 levels. The children with stable asthma were further divided into the mild, moderate, and severe groups according to their degree of asthma. A pulmonary function meter was used to assess the pulmonary function indexes: percentage of forced expiratory volume in 1 sec/predictive value (FEV1%pred), forced vital capacity (FVC), forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC), peak expiratory flow (PEF), and maximal voluntary ventilation (MVV). The children's quality (QOL) of life with asthma was evaluated by their activities of daily living (ADLs) and Medical Research Council (MRC) scores. Pearson correlation analysis was applied to analyze the correlations of serum vitamin A and 25OHD3 levels with FEV1%pred, FVC, FEV1/FVC, PEF, MVV, ADL, and MRC. RESULTS: Serum vitamin A and 25OHD3 levels were lower in children with stable asthma than those who were in the control group (Pâ<â.05). The severe group showed the lowest FEV1%pred, FVC, FEV1/FVC, PEF, MVV, and ADL scores, and the highest MRC score compared to the mild and moderate groups (all Pâ<â.05). Serum vitamin A and 25OHD3 levels were positively correlated with pulmonary function and ADL score in children with stable asthma, while serum vitamin A and 25OHD3 levels were negatively correlated with MRC score (all Pâ<â.05). In the case group, serum vitamin A and 25OHD3 levels were positively correlated with serum calcium and phosphorus levels (all Pâ<â.05). CONCLUSION: These findings indicate that increased serum vitamin A and 25OHD3 levels reflect good pulmonary function and good QOL in children with stable asthma.
