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

OBJECTIVETo investigate the clinicopathologic significance of pin1 and PR in patients with endometrial adenocarcinoma.

METHODSThe expression of pin1 and PR were investigated by immunohistochemistry in a total of 50 endometrial adenocarcinoma specimens.

RESULTSPin1 was over expressed in 66% (33/50) of the cases. The expression rate decreased gradually with tumor differentiation(P<0.05). In addition, pin1 expression was negatively correlated with lymph node metastasis and invasive depth of myometrium. Moreover, pin1 was positively correlated with PR expression.

CONCLUSIONOur results suggest that pin1 may play important roles in the tumorigenesis and migration of endometrial cancer. Pin1 expression may be considered as a prognostic marker as PR in patients with endometrial cancer.

Adult ; Biomarkers, Tumor ; metabolism ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase ; metabolism ; Receptors, Progesterone ; metabolism ; Uterine Neoplasms ; metabolism ; pathology

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 study the expression and relationship of Pin1 and CyclinD1 in adult papilloma of larynx, and the effect of both in laryngeal papilloma's canceration. METHOD: Ninety-two cases of paraffin section with immunoperoxidase (SP) staining method was used to detect the distribution of Pin1 and CyclinD1 in 10 cases of laryngeal normal epithelial tissue, 39 cases of laryngeal papilloma, 27 cases of laryngeal papilloma with middle, severe atypical hyperplasia and 16 cases of laryngeal carcinoma. RESULT: The distribution of Pin1 and CyclinD1 increased gradually from laryngeal normal epithelial tissue to laryngeal carcinoma (P<0.05); No difference of the expression of CyclinD1 (not including Pin1, for Pin1, P=0.009) was found between laryngeal papilloma and laryngeal papilloma with middle, severe atypical hyperplasia (P>0.0125), but there had significant difference of the expression of Pin1 and CyclinD1 among the rest groups; There was significantly direct correlation between the expression of Pin1 and CyclinD1 (P<0.05). CONCLUSION The hyper-expressions of Pin1 and CyclinD1 may play a key role in laryngeal papilloma's malignant change. Pin1 up-regulating the expressions of cyclinD1 possibly participate in its malignant change.
Adult ; Aged ; Cyclin D1 ; metabolism ; Female ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; NIMA-Interacting Peptidylprolyl Isomerase ; Papilloma ; metabolism ; pathology ; Peptidylprolyl Isomerase ; metabolism ; Young Adult

Pin1 is a phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, which specifically catalyzes the amide bond isomerization of phosphoserine-proline or phosphothreonine-proline in mitotic phosphoproteins. Pin1 induces the conformational changes to control the function of phosphoproteins. Depletion of Pinl on various human cancer cell lines cause mitotic arrest and apoptosis. Pin1 is an attracting therapeutic target for anticancer and its inhibitors might be potential anticancer drug. In this review, Pin1 inhibitors and the catalytic mechanism, the biological function of Pin1 and its role in oncogenesis are summarized.
Apoptosis ; Enzyme Inhibitors ; chemical synthesis ; pharmacology ; Humans ; Mitosis ; drug effects ; NIMA-Interacting Peptidylprolyl Isomerase ; Neoplasms ; enzymology ; Peptidylprolyl Isomerase ; antagonists & inhibitors ; metabolism ; Phosphoproteins ; chemistry ; metabolism ; Phosphorylation ; drug effects ; Signal Transduction ; drug effects

Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) belongs to peptidyl-prolyl cis-trans isomerase (PPIase) and is a novel promising anticancer target. Based on the lead structure of benzophenone, a series of novel diarylether derivatives containing a pyrimidine ring were designed and synthesized. The inhibitory activities on Pin1 of compounds 5a-5d and 6a-6i were evaluated by a protease-coupled enzyme assay. Of all the evaluated compounds, 6 compounds displayed inhibitory activities. Molecular docking was performed using FlexX algorithm to explore the binding mode of the active molecules.
Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Ethers ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Molecular Docking Simulation ; Molecular Structure ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase ; antagonists & inhibitors ; metabolism ; Pyrimidines ; chemistry ; Structure-Activity Relationship

Malignant tumor, one of the most refractory diseases, plays a threaten role in human health, the therapy and research on malignant tumor have taken a long way to go. The anti-tumor drugs which are the essential therapy strategies upgrade with the development of new anti-tumor targets and the research on tumor pathogenesis. Aurora kinase and Pin1, the novel anti-tumor targets, maintain the important relationship with tumor. Many new compounds designed on these targets have excellent anti-tumor effects and also enter into phase I or phase II clinical trial.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Aurora Kinases ; Humans ; NIMA-Interacting Peptidylprolyl Isomerase ; Naphthoquinones ; pharmacology ; Neoplasms ; metabolism ; pathology ; Peptidylprolyl Isomerase ; antagonists & inhibitors ; metabolism ; Piperazines ; pharmacology ; Protein-Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism

OBJECTIVETo investigate the expression of Pin1, beta-catenin and cyclin D1 in salivary adenoid cystic carcinomas (SACC) and to evaluate the role of beta-catenin and Pin1 in SACC carcinogenesis.

METHODSThe expressions of Pin1, beta-catenin and cyclin D1 were examined in the specimens of 65 patients with SACC by immunohistochemistry, and Pin1 protein and mRNA expressions detected by Western blot and RT-PCR in four SACC cell lines.

RESULTSPin1 was overexpressed in 51 cases of ACC (78%), and 41 (63%) cases showed positive immunoreactivity for cyclin D1 protein in the nuclear fraction in tumor tissues. Fourteen (22%) cases showed positive immunoreactivity for beta-catenin protein in the nuclear/cytoplasmic fraction in tumor tissues, 6 of which exhibited quite evident expression of beta-catenin in nucleolus. The expression of membranous beta-catenin was down-regulated in most of the patients with lymph node metastasis (11/14).

CONCLUSIONSThe results suggest that Pin1 and beta-catenin signalling pathway were activated in SACC and might play a pivotal role in SACC carcinogenesis and metastasis.

Carcinoma, Adenoid Cystic ; metabolism ; pathology ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Humans ; Lymphatic Metastasis ; NIMA-Interacting Peptidylprolyl Isomerase ; Neoplasm Invasiveness ; Peptidylprolyl Isomerase ; metabolism ; Salivary Gland Neoplasms ; metabolism ; pathology ; beta Catenin ; 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

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