OBJECTIVETo explore the effect of silence of Pin1 expression on hyperoxia-induced apoptosis in alveolar epithelial cells A549.

METHODSA549 cells were divided into four groups: control, hyperoxia, negative lentivirus and Pin1-shRNA hyperoxia. The hyperoxia group was exposed to a mixture of 95%O2 and 5%CO2 for 10 minutes. Then cells were cultured in a closed environment. After 24 hours, the changes of morphology were observed under an inverted microscope. Cell apoptosis was detected by flow cytometry (FCM). The expression of X-linked inhibitor of apoptosis protein (XIAP) and Caspase-9 were detected by immunohistochemistry. The production of reactive oxygen species (ROS) and cellular mitochondria membrane potential (△Ψm) were determined by fluorescence microscopy.

RESULTSUnder the inverted microscope, the A549 cells grew slowly and the changes in morphology of the cells were most obvious in the hyperoxia and negative lentivirus groups. The changes in morphology of A549 cells were obviously improved in the Pin1-shRNA hyperoxia group. The FCM results showed that the apoptosis rate of A549 cells increased, Caspase-9 expression increased, XIAP expression decreased, mitochondrial ROS production increased and mitochondrial membrane potential decreased in the hyperoxia and negative lentivirus groups compared with the control group (P<0.05). Compared with the hyperoxia and negative lentivirus groups, the apoptosis rate of A549 cells decreased, Caspase-9 expression decreased, XIAP expression increased, mitochondrial ROS production decreased and mitochondrial membrane potential increased in the Pin1-shRNA hyperoxia group (P<0.05), although the levels of the indexes did not reach to those of the control group.

CONCLUSIONSSilencing of Pin1 could suppress hyperoxia-induced apoptosis of A549 cells.

Apoptosis ; Caspase 9 ; genetics ; Humans ; Hyperoxia ; pathology ; Membrane Potential, Mitochondrial ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase ; physiology ; Reactive Oxygen Species ; metabolism ; X-Linked Inhibitor of Apoptosis Protein ; genetics

In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P < 0.05). The expression of Pin1 protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer (P < 0.05). No significant difference in the Pin1 expression was found between disease stages (FIGO), pathological grades or pelvic lymph node metastasis status (P > 0.05). The expression of Pin1 was significantly higher in adenocarcinoma than in squamous carcinoma of the uterine cervix (P < 0.05). In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P < 0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.
Cervical Intraepithelial Neoplasia/metabolism ; Ki-67 Antigen/*biosynthesis ; Ki-67 Antigen/genetics ; Peptidylprolyl Isomerase/*biosynthesis ; Peptidylprolyl Isomerase/genetics ; Tumor Markers, Biological ; Uterine Cervical Neoplasms/*metabolism

OBJECTIVE: To investigate the effect of yizhi jiannao granule concentration fluid (YCF) on the expression of peptidyl-prolyl-cis-trans isomerase A (Pin1) and high mobility group box 1 (HMGB1) mRNA in the hippocampus of senescence accelerated mice Senile-Prone8(SAMP8). METHODS: Six-month old SAMP8 mice were randomly divided into a YCF group and a model group. Six-month old SAMP8 mice were served as a normal control group. The YCF group was ravaged, while the model group and the normal control group were gavaged with double-distilled water for 8 weeks. The hippocampus was taken out for examination. The expression of Pin1 and HMGB1 mRNA was measured by RT-PCR. RESULTS: In the YCF group, the level of Pin1 mRNA increased, and the level of HMGB1 mRNA decreased compared with that of the model group. CONCLUSION Yizhi jiannao granules can prevent Alzheimer's disease by increasing the Pin1 level and decreasing the HMGB1 level.
Aging ; drug effects ; metabolism ; Alzheimer Disease ; metabolism ; Animals ; Drugs, Chinese Herbal ; pharmacology ; HMGB1 Protein ; genetics ; metabolism ; Hippocampus ; metabolism ; Male ; Mice ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism

OBJECTIVE: To detect the expression of peptidylprolyl cis/trans isomerase NIMA-interacting l (pin1 mRNA) in the circulation of non-small cell lung cancer (NSCLC) and to investigate the effect of ligating pulmonary vein first or ligating pulmonary artery first during operation on haematogenous dissemination of cancer cells. METHODS: Twenty-six consecutive patients with NSCLC who underwent surgical resection with curative intention were randomly assigned into pulmonary artery first-ligation group (PA group) and pulmonary vein first-ligation group (PV group). Blood samples were collected just before and 7 days after the operation. During the lobectomy, blood samples of the proximal part and distal part of the pulmonary vein when it was ligated were collected. Another 10 patients with benign lung disease served as control subjects undergoing surgical resection, and 10 healthy persons served as negative controls. All blood samples were subjected to real-time RT-PCR with pin1 mRNA as the marker. RESULTS: Compared with the benign lung disease and healthy persons, pin1 mRNA in NSCLC was overexpressed (1.45 to approximately 29.86 vs.0.83 to approximately 1.26 vs 1, P<0.05). pin1 mRNA in stage III NSCLC and lymph node positive were significantly higher than in stage I to approximately II and lymph node negative(18.48+/-1.64 vs.10.57+/-1.05, P<0.05;18.93+/-2.10 vs.10.02+/-1.23, P<0.05). Expression of pin1 mRNA in the distal part of the pulmonary vein was significantly higher than that of the proximal part (30.56+/-1.37 vs.20.31+/-1.48, P<0.05); the expression 7 days after the operation was significantly lower than that of preoperation (20.68+/-1.17 vs.29.43+/-2.62, P<0.05). There was no significant difference between the PA group and PV group (9.95+/-0.91 vs.14.71+/-1.64, P>0.05; 16.84+/-2.36 vs.13.36+/-1.78, P>0.05). CONCLUSION pin1 mRNA was overexpressed in the circulation of NSCLC. Ligation of pulmonary vein before the ligation of the pulmonary artery may decrease the expression of pin1 mRNA in the circulation, which can prevent the release of tumor cells into the bloodstream.
Carcinoma, Non-Small-Cell Lung ; blood ; surgery ; Female ; Humans ; Ligation ; methods ; Lung Neoplasms ; blood ; surgery ; Male ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase ; genetics ; metabolism ; Pulmonary Artery ; surgery ; Pulmonary Surgical Procedures ; methods ; Pulmonary Veins ; surgery ; RNA, Messenger ; genetics ; metabolism

OBJECTIVETo study the expression of peptidyl-prolyl cis/trans isomerase (PPIase or Pin1) in malignant hematopoietic cells and its relation with cell cycle.

METHODSRealtime quantitative PCR with fluorescence probe hybridization was used to measure expression of Pin1 mRNA in malignant hematopoietic cell lines and normal mononuclear cells separated from bone marrow. HeLa cells were blocked with Thymidine and Nocodazole in different cell phases and then the expression of Pin1 mRNA and protein were detected by realtime-PCR and immunoblotting.

RESULTSThe expression of Pin1 in malignant hematopoietic cell lines was significantly higher than that in normal controls (0.339 +/-0.093 compared with 0.038 +/-0.005, P<0.01). Its expression in myeloid malignant hematopoietic cell lines was significantly higher than that in normal controls (0.388 +/-0.115 compared with 0.038 +/-0.005, P<0.01) and so was the malignant lymphocytic cell lines (0.226 +/-0.166 compared with 0.038 +/-0.005, P<0.01). The expression of Pin1 was closely correlated with cell cycle. It was the highest in G1 phase and the lowest in S phase (110.762 +/-16.737 compared with 4.080 +/-0.634, P<0.01).

CONCLUSIONPin1 is overexpressed in malignant hematopoietic cell lines and its expression is different during cell cycle that is highest in G1 phase and lowest in S phase.

Cell Cycle ; physiology ; G1 Phase ; Humans ; Leukemia, Lymphoid ; enzymology ; pathology ; Leukemia, Myeloid ; enzymology ; pathology ; Peptidylprolyl Isomerase ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; S Phase ; Tumor Cells, Cultured

MicroRNAs (miRNAs) are conserved small non-coding RNAs that play an important role in the regulation of gene expression and participate in a variety of biological processes. The biogenesis of miRNAs is tightly controlled at multiple steps, such as transcription of miRNA genes, processing by Drosha and Dicer, and transportation of precursor miRNAs (pre-miRNAs) from the nucleus to the cytoplasm by exportin-5 (XPO5). Given the critical role of nuclear export of pre-miRNAs in miRNA biogenesis, any alterations of XPO5, resulting from either genetic mutation, epigenetic change, abnormal expression level or posttranslational modification, could affect miRNA expression and thus have profound effects on tumorigenesis. Importantly, XPO5 phosphorylation by ERK kinase and its cis/trans isomerization by the prolyl isomerase Pin1 impair XPO5's nucleo-to-cytoplasmic transport ability of pre-miRNAs, leading to downregulation of mature miRNAs in hepatocellular carcinoma. In this review, we focus on how XPO5 transports pre-miRNAs in the cells and summarize the dysregulation of XPO5 in human tumors.
Carcinoma, Hepatocellular ; genetics ; metabolism ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Humans ; Karyopherins ; chemistry ; metabolism ; physiology ; Liver Neoplasms ; genetics ; metabolism ; MicroRNAs ; chemistry ; metabolism ; NIMA-Interacting Peptidylprolyl Isomerase ; Neoplasms ; genetics ; metabolism ; RNA Precursors ; chemistry ; metabolism ; RNA Transport