ABSTRACT
Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.
Subject(s)
Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Lung Neoplasms/pathology , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , Up-Regulation/genetics , Adult , Aged , Animals , Apoptosis/genetics , Base Sequence , Carcinogenesis/genetics , Carcinogenesis/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Knockdown Techniques , Humans , Male , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Middle Aged , Models, Biological , Protein Binding , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
This study was designed to provide further understanding of transcorneal mechanism of nanostructured lipid carriers (NLC). NLC labeled with fluorescent marker rhodamine B or coumarin-6 were produced by a melt emulsification method. By confocal laser scanning microscopy (CLSM), the interaction of NLC with corneal epithelia was traced and evaluated in rabbits in vivo. Thermal stability of the markers and the amorphous state were detected using thermogravimetric analysis (TGA) and differential scanning calorimeter (DSC). The labeled NLC were characterized to be solid spherical in shape with an average diameter of 70 nm and zeta potential of -8 mV by transmission electron microscopy and dynamic light scattering, respectively. CLSM results demonstrated NLC were not directly internalized by corneal epithelia, whereas the markers themselves transferred from NLC to corneal epithelia with subsequent staining of intracellular lipophilic compartments. Furthermore, the in vitro release study using liposome dispersions as mimic biomembranes demonstrated an efficient transfer of fluorescence marker into the liposomes. This implied the deceptive particle uptake was due to a collision-induced process, during which the rapid transfer of fluorescence marker occurred by forming a complex between the nanoparticles and the biomembranes. Thus, these evidences provide further insights into NLC as an ocular delivery system.
Subject(s)
Lipids/chemistry , Nanostructures/chemistry , Animals , Calorimetry, Differential Scanning , Epithelium, Corneal/metabolism , Liposomes/chemistry , Microscopy, Confocal , Microscopy, Electron, Transmission , Nanostructures/administration & dosage , Nanostructures/ultrastructure , Rabbits , Rhodamines/administration & dosage , Rhodamines/chemistryABSTRACT
OBJECTIVE: To optimize the process of extracting total flavonoids from Tagetes erecta. METHODS: The influential factors were extraction temperature, ethanol concentration, reflux time and solvent volume fold. The evaluating indicator was the extraction rate of total flavonoids from Tagetes erecta. The central composite design-response surface methodology was used to optimize the process and the prediction was carried out. RESULTS: The optimum conditions of extraction were 80% ethanol, 2.5 hours for reflux, 35 volume folds of solvent and 70 degrees C. CONCLUSION: It shows that the optimum model is simple and highly predictive.
