RESUMO
Long noncoding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer (PCa) as competitive endogenous RNA. The present study aimed to investigate the molecular mech--anisms of lncRNA small nucleolar RNA host gene 16 (SNHG16) in the proliferation and metastasis of PCa cells. Cancer tissues and adjacent normal tissues were collected from 80 patients with PCa who did not receive any treatment. Reverse transcriptionquantitative PCR analysis was performed to detect the expression levels of SNHG16, hsamicroRNA (miRNA/miR)3733p and transforming growth factorß receptor type 2 (TGFßR2), and Spearman's correlation coefficient analysis was performed to assess the correlations between these molecules. Furthermore, the effects of SNHG16 knockdown and overexpression on the biological functions of DU145 PCa cells and TGFßR2/SMAD signaling were analyzed. The dualluciferase reporter assay was performed to assess the associations between SNHG16 and miR3733p, and TGFßR2 and miR3733p, the effects of which were verified via rescue experiments. The results demonstrated that the expression levels of SNHG16 and TGFßR2 were significantly upregulated in PCa tissues, whereas miR3733p expression was significantly downregulated (P<0.001). In addition, negative correlations were observed between SNHG16 and miR3733p (rho, 0.631) and miR3733p and TGFßR2 (rho, 0.516). Overexpression of SNHG16 significantly promoted the proliferation, migration and invasion of PCa cells (P<0.05), and significantly increased the protein expression levels of TGFßR2, phosphorylated (p)SMAD2, pSMAD3, cMyc and E2F4 (P<0.001). Notably, the results revealed that miR3733p is a target of SNHG16, and miR3733p knockdown rescued short hairpin (sh)SNHG16suppressed cellular functions by promoting TGFßR2/SMAD signaling. The results also revealed that miR3733p targets TGFßR2. Notably, transfection with miR3733p inhibitor rescued shTGFßR2suppressed cell proliferation and migration. Taken together, the results of the present study suggest that SNHG16 promotes the proliferation and migration of PCa cells by targeting the miR3733p/TGFßR2/SMAD axis.
Assuntos
MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Longo não Codificante/genética , Fator de Crescimento Transformador beta/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Regulação para CimaRESUMO
PURPOSE: The most common disadvantage of 11C-choline positron emission tomography and computed tomography (PET/CT) in diagnosing early-stage prostate cancer (PCa) is its poor sensitivity. In spite of many efforts, this imaging modality lacks the ideal parameter of choline metabolism for the diagnosis of PCa, and the single metabolic parameter, that is, maximal standardized uptake value (SUVmax), based on this imaging modality is insufficient. 11C-choline PET/CT-based multi-metabolic parameter combination can help break this limitation. MATERIALS AND METHODS: Before surgery, SUVmax of choline, which is the most common metabolic parameter of 11C-choline PET/CT, mean standardized uptake value (SUVmean), prostate-to-muscle (P/M) ratio, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from 74 patients with histologically proven PCa were quantified. A total of 13 patients with focal chronic prostatitis without severe features and 30 patients with benign prostate hyperplasia were used for comparison. Univariable and multivariable analyses were performed to compare the patient characteristics and metabolic parameters of 11C-choline PET/CT. The performance of single parameters and the combination of parameters were assessed by using logistic regression models. RESULTS: The comparable c-statistics, which mean the area under the ROC curve in the logistic regression model, of SUVmax, SUVmean, and P/M ratio are 0.657, 0.667, and 0.672, respectively. The c-statistic significantly rose to 0.793 when SUVmax and SUVmean were combined with the P/M ratio. This parameter combination performed the best for PCa cases with all biochemical recurrence risks and for PCa patients grouped by different risk. The greatest improvement over a single parameter, such as P/M ratio, was noted in the group of low-risk PCa, with values of 0.535 to 0.772 for the three-parameter combination. And in the histopathological level, the Ki-67 index is positively correlated with the P/M ratio (r=0.491, p=0.002). CONCLUSION: P/M ratio is a more ideal parameter than SUVmax as a single parameter in early-stage PCa diagnosis. According to our data, the combination of SUVmax, SUVmean, and P/M ratio as a composite parameter for diagnosis of early stage PCa improves the diagnostic accuracy of 11C-choline PET/CT.
RESUMO
Nanoparticular drug delivery system (NDDS) has great potential for enhancing the efficacy of traditional chemotherapeutic drugs. However, it is still a great challenge to fabricate a biocompatible NDDS with simple structure capable of optimizing therapeutic eï¬cacy, such as high tumor accumulation, suitable drug release profile (e.g. no premature drug leakage in normal physiological conditions while having a rapid release in cancer cells), low immunogenicity, as well as good biocompatibility. In this work, a simple core/shell structured nanoparticle was fabricated for prostate cancer treatment, in which a mesoporous silica nanoparticle core was applied as a container to high-efficiently encapsulate drugs (doxorubicin, DOX), CaCO3 interlayer was designed to act as sheddable pH-sensitive gatekeepers for controlling drug release, and cancer cell membrane wrapped outlayer could improve the colloid stability and tumor accumulation capacity. In vitro cell experiments demonstrated that the as-prepared nanovehicles (denoted as DOX/MSN@CaCO3@CM) could be efficiently uptaken by LNCaP-AI prostate cancer cells and even exhibited a better anti-tumor efficiency than free DOX. In addition, Live/Dead cell detection and apoptosis experiment demonstrated that MSN/DOX@CaCO3@CM could effectively induce apoptosis-related death in prostate cancer cells. In vivo antitumor results demonstrated that DOX/MSN@CaCO3@CM administration could remarkably suppress the tumor growth. Compared with other tedious approaches to optimize the therapeutic eï¬cacy, this study provides an effective drug targeting system only using naturally biomaterials for the treatment of prostate cancer, which might have great potential in clinic usage.
Assuntos
Membrana Celular/metabolismo , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Dióxido de Silício/química , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose , Proliferação de Células , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Porosidade , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A nonintrusive method for flow gas temperature measurement using differential optical absorption spectroscopy (DOAS) was demonstrated. A temperature-dependent spectra (TDS) originated from the DOAS spectra of sulfur dioxide (SO2) in the wavelength range of 276-310 nm was introduced, and the relationship between the TDS and the temperature was built through experimental calibration process. This relationship is found to be independent of SO2 concentration and can be used for temperature measurements. The experimental results indicated that the precision of the TDS method is < ± 0.3% for SO2 concentrations higher than 150 ppm with the optical path length of 170 mm. For lower concentrations, the precision is estimated to be ± 0.4% at 1 ppm. The relative deviation between the temperature measured by the TDS method and that measured by a thermocouple is within 3% in the temperature range of 298-750 K, and the TDS method has a quicker response to the fast-changing temperature than the thermocouple.