ABSTRACT
MicroRNA-26 (miR-26) has been reported to be connected with tumor progression. MicroRNA-4465 (miR-4465) was one member of miR-26 family, however, the role of miR-4465 in non-small cell lung cancer (NSCLC) was unknown. This study was aimed to explore the function of miR-4465 and investigate whether miR-4465 can be a potential target for treating human NSCLC. QRT-PCR was applied to evaluate the miR-4465 expression levels in NSCLC cells. Then, we demonstrated the role of miR-4465 in NSCLC cells biological characteristics through detecting proliferation, migration and invasion. Luciferase reporter assay and TargetScan were applied to explore the potential target gene of miR-4465. In this study, we found that the miR-4465 expression levels in NSCLC cell lines were significantly reduced when compared to the normal human bronchial epithelial cell lines. And, over expression of miR-4465 could restrain the proliferation, migration and invasion of NSCLC. Moreover, MiR-4465 reduced EZH2 protein expression through the binding sites in 3' -UTR of the EZH2 mRNA, indicating EZH2 may be a direct target gene of miR-4465. Conclusively, miR-4465 suppressed cancer cells proliferation and metastasis by directly targeting the oncogene EZH2 and it may serve as a new potential therapeutic target in NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Enhancer of Zeste Homolog 2 Protein/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Oncogenes/genetics , 3' Untranslated Regions/genetics , A549 Cells , Cell Line , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/genetics , HEK293 Cells , Humans , RNA, Messenger/geneticsABSTRACT
Forkhead box R2 (FOXR2), a member of the FOX gene family, has not been very well investigated for its role in cancer. A recent study has shown that FOXR2 is highly expressed in breast cancer samples and is associated with poor prognosis. In addition, FOXR2 was identified as an oncogene in medulloblastoma. Nevertheless, whether FOXR2 plays a role in colorectal cancer (CRC) remains unclear. In the present study, we conducted several in vitro and in vivo studies to investigate the expression and effect of FOXR2 in CRC. The study results demonstrated that FOXR2 was upregulated in CRC tissues and cells. Downregulation of FOXR2 inhibited CRC cell proliferation, invasion, and the epithelial-mesenchymal transition (EMT) phenotype in vitro and also suppressed CRC cell growth and metastasis in vivo. Furthermore, downregulation of FOXR2 remarkably reduced the protein expression of Shh, Gli1, and Ptch1 in SW480 cells. Taken together, our data suggested that FOXR2 significantly promoted proliferation, invasion, and EMT of CRC cells. All these findings provided evidence for the role of FOXR2 as an oncogene in CRC development.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Forkhead Transcription Factors/genetics , Animals , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colorectal Neoplasms/metabolism , Disease Models, Animal , Down-Regulation , Gene Expression , Hedgehog Proteins/metabolism , Heterografts , Humans , Male , Mice , Neoplasm Metastasis , Signal TransductionABSTRACT
Objective. To observe the effect of sustained +Gx exposure on contractility of rat diaphragm and explore its mechanism. Method. Forty-two male Wistar rats were randomly divided into control group (underwent +1 Gx exposure, n=21) and experiment group (underwent +15 Gx for 3 min, n=21). The tension of rat diaphragm in vivo, contents of nucleoside phosphates and lactic acid in diaphragm and ultrastructure of diaphragm were measured and observed respectively. Result. 1) Compared with pre- +Gx, low-frequency tension of diaphragm of experiment group decreased significantly (P<0.01), whereas high-frequency tension did not significantly decrease after +Gx (P>0.05). As to the control group, however, the tension of diaphragm tested at a wide range of frequencies was almost unchanged (P>0.05). 2) Compared with control group, ATP decreased (P<0.01), while ADP and lactic acid contents in diaphragm increased significantly (P<0.05 and P<0.01) after +Gx in experiment group. In addition, ratios of ADP/AMP and AMP/ATP increased significantly (P<0.01). 3) After +Gx exposure, hypoxic changes in ultrastructure of rat diaphragm occurred in experiment group, but not in control group. Conclusion. Sustained +Gx exposure could cause diaphragm muscle fatigue, which was possibly due to changes in energy metabolism and ultrastructure of rat diaphragm induced by hypoxia under +Gx stress.
Subject(s)
Diaphragm/physiology , Diaphragm/ultrastructure , Energy Metabolism/physiology , Hypergravity , Muscle Contraction/physiology , Muscle Fatigue/physiology , Acceleration , Adenosine Diphosphate/metabolism , Adenosine Monophosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Diaphragm/metabolism , Hypoxia , Lactic Acid/metabolism , Male , Microscopy, Electron , Rats , Rats, WistarABSTRACT
Objective. To study the anti +Gx respiratory maneuver and its training method. Method. Seven young male subjects undertook the anti +Gx respiratory maneuver training. Their +Gx tolerances were examined on human centrifuge before and after training. The change of respiratory type, breath rate, electrocardiogram, heart rate, arterial oxygen saturation (SaO2), subjective symptom and vision were real-time monitored during the +Gx tolerance examination. Result. Compared with pre-training, the +Gx tolerance increased after training (P<0.05). Dyspnea and chest pain disappeared or obviously lightened and the magnitude of decrease of SaO2 decreased significantly (P<0.05). Conclusion. The above results suggested that the anti +Gx respiratory maneuver can effectively eliminate or alleviate dyspnea and chest pain induced by +Gx stress and increase human +Gx tolerance.
Subject(s)
Adaptation, Physiological , Breathing Exercises , Hypergravity/adverse effects , Inservice Training , Respiration , Aerospace Medicine , Centrifugation , Chest Pain/etiology , Chest Pain/prevention & control , Dyspnea/etiology , Dyspnea/prevention & control , Heart Rate , Humans , Hypoxia/etiology , Hypoxia/prevention & control , Male , Oxygen/blood , Physical EnduranceABSTRACT
Objective. To observe the changes of energy metabolism of brain tissue in rats under +Gx loads, and to explore its possible role in changes of brain function and work efficiency induced by +Gx stress. Method. Forty-five male Wistar rats were randomly divided into control, +5 Gx, +10 Gx, +15 Gx and +20 Gx group. Each group was exposed to the corresponding G value for 3 min. After that, cortical adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactic acid (LA) content, lactate dehydrogenase (LDH) activity were measured. Result. Compared with the control group, the cortical (LA) content increased significantly after +5 Gx, +10 Gx, +15 Gx and +20 Gx exposure (P<0.01). Cortical ADP content and ratio of ADP/AMP and AMP/ATP increased significantly after +10 Gx, +15 Gx and +20 Gx exposure (P<0.01), whereas ATP content, energy charge and LDH activity decreased significantly (P<0.05 or 0.01). Cortical AMP content increased significantly after +15 Gx and +20 Gx exposure (P<0.05 and 0.01). Conclusion. It is suggested that +Gx load can result in obvious depression of brain energy metabolism, which could be an important reason for the change of brain function and work efficiency induced by +Gx stress.
