Cardiovascular Diseases/genetics* ; Humans ; STAT3 Transcription Factor

OBJECTIVE: To investigate the effect of miR-29b-3p on apoptosis and proliferation of acute myeloid leukemia (AML) cells by targeting signal transducer and activator of transcription 3 (STAT3). METHODS: TargetScan and miRanda online databases were used to predict the binding sites of miR-29b-3p and STAT3 3'UTR. The targeting relationship between them was estimated by Dual-Luciferase reporter assay experiment. After miR-29b-3p over-expression, qPCR and Western blot were used to detect the expression of STAT3 mRNA and proteins, flow cytometry to determine the apoptosis of AML cells, and MTS to detect the changes of cell proliferation in each group. RESULTS: Dual-Luciferase reporter assay confirmed that STAT3 was the target gene of miR-29b-3p. After miR-29b-3p overexpression, the expression of STAT3 mRNA and protein decreased. Compared with the control groups, the proliferation of AML cells in the overexpression group decreased and the apoptosis increased (P<0.05). CONCLUSION MiR-29b-3p can inhibit the proliferation and induce apoptosis of AML cells by down-regulating STAT3.
Apoptosis ; Cell Proliferation ; Humans ; Leukemia, Myeloid, Acute/genetics* ; MicroRNAs/genetics* ; STAT3 Transcription Factor/genetics*

A boy, aged 4 years and 6 months, had disease onset of fever, cough, pale complexion, and weakness, with hepatosplenomegaly, lymphadenectasis, and pancytopenia. He had been having repeated respiratory and digestive tract infections. Gene detection showed a pathogenic heterozygous mutation, c.C2147 > T(p.T716M), in the
Child, Preschool ; Fever ; Heterozygote ; Humans ; Immune System Diseases/genetics* ; Male ; Mutation ; STAT3 Transcription Factor/genetics* ; Syndrome

OBJECTIVE: To investigate the expression of STAT3 gene in patients with acute myeloid leukemia and its correlation with clinical characteristics. METHODS: The real-time quantitative RT-PCR was used to detect the level of STAT3 mRNA in bone marrow samples from 38 newly diagnosed patients with acute myeloid leukemia(AML), and its relevance with clinical characteristics and prognosis were statistically analyzed. Western blot was employed to detect the STAT3 protein level in AML patients. The bone marrow cells from 15 healthy subjects were used as control. RESULTS: At the mRNA level, the expression level of STAT3 in the AML group was significantly higher than that in control group (P<0.05). The level of STAT3 in AML group correlated positively with the risk factors of patients (P<0.01，r=0.592）. The STAT3 expression level in the high-risk group was statistically higher than that in the standard-risk group and the control group (P<0.01，P<0.01). Furthermor, there was no statistical difference between the sub-groups of AML (P>0.05). The median survival time of patients in STAT3 low expression group was logner than that in high expression group, but the difference was not statistically significant (P>0.005). The level of STAT3 protein in AML patients was significantly higher than that in control group (P<0.05）. CONCLUSION The STAT3 gene is highly expressed in AML patients, which may be used as a predictor for high-risk of AML.
Bone Marrow ; Humans ; Leukemia, Myeloid, Acute ; Prognosis ; RNA, Messenger ; STAT3 Transcription Factor ; genetics

Cell Line, Tumor ; Gene Silencing ; Hep G2 Cells ; Humans ; RNA, Small Interfering ; STAT3 Transcription Factor ; genetics

Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of clonal expansion of cytotoxic T- or NK-cells in blood and bone marrow, and often associated with autoimmune disorders. According to the current WHO classification of the hematopoietic and lymphoid tissue tumors, the clonal LGL expansions are further classified as T-cell large granular lymphocytic leukemia (T-LGLL), chronic lymphoproliferative disorders of NK cells (CLPD-NK) and aggressive NK cell leukemia. Since there is a general lack of awareness of this disease, some patients may be misdiagnosed or some cases may be missed when diagnosis was done. At present, the pathogenesis of LGLL remains incomplete and unclear, and the therapeutic effects are unsatisfactory. For this reason, it is necessary to find prognostic marks and therapeutic targets of this disease. The constitutive activation of JAK/STAT pathway has been claimed to be involved in the development of LGLL. Recently, the somatic mutations in the SH2 domain of STAT3 in LGLL are frequently observed, which lead to the activation of JAK/STAT pathway. STAT3 is the first molecular markers that are highly specific for LGLL, and STAT3 mutations have been rarely detected in other tumor types studied, thus the STAT3 mutations can be used as molecular markers for LGLL diagnosis and can provide a novel therapeutic target for patients with LGLL.
Humans ; Janus Kinases ; genetics ; metabolism ; Leukemia, Large Granular Lymphocytic ; genetics ; metabolism ; Mutation ; STAT3 Transcription Factor ; genetics ; metabolism ; Signal Transduction

OBJECTIVE: To detect the expression of JAK2/STAT3 mRNA in peripheral blood T cells from the patients with chronic idiopathic thrombocytopenic purpura（CITP）, and to explore the relationship between JAK2/STAT3 mRNA and CITP. METHODS: CITP group and healthy control group were set in this study, The JAK2/STAT3 mRNA expression level in peropheral blood T cells of 2 groups was detected with the RT-PCR and agarose gel electrophoresis. RESULTS: JAK2 mRNA expression level in CITP group was significantly higher than that in control group（P<0.01）, the STAT3 mRNA expression level in CITP group was also higher than control group（P<0.01）, The JAK2/STAT3 mRNA expression level of CITP patiants increased obviously compared with control group. CONCLUSION The expression level of JAK2/STAT3 mRNA increases signficanlty in chronic ITP patients, which involves in pathogenesis of CITP.
Chronic Disease ; Humans ; Janus Kinase 2 ; genetics ; Purpura, Thrombocytopenic, Idiopathic ; RNA, Messenger ; STAT3 Transcription Factor ; genetics ; T-Lymphocytes

OBJECTIVE: To study the effects of oligodeoxynucleotides complementary Stat3 on apoptosis in laryngeal carcinoma Hep-2 cell. METHOD: Oligodeoxynucleotides complementary Stat3 was designed, which was transferred into laryngeal carcinoma Hep-2 cell by lipofection. Expression of Stat3 and p-Stat3 were detected by Western blot and PCR. MTT was used to observe the growth-inhibiting ratio. DNA ladder, AO/EB and FCM were used to observe the apoptosis of laryngeal carcinoma cell Hep-2 in vitro. RESULT: Western blot and PCR results demonstrated that oligodeoxynucleotides complementary Stat3 could significantly inhibit the expression of Stat3 and p-Stat3 in Hep-2 cell. MTT results showed that it could significantly suppress the growth of Hep-2 cell. The DNA ladder, AO/EB and FCM results showed it could inhibit the expression of Stat3 and induce the apoptosis of Hep-2 cell in a concentration-dependent manner. CONCLUSION Oligodeoxynucleotides complementary Stat3 could induce the apoptosis and suppress cell proliferation in laryngeal carcinoma Hep-2 cell.
Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Oligodeoxyribonucleotides ; genetics ; pharmacology ; STAT3 Transcription Factor ; genetics ; Transfection

OBJECTIVES: Glioma is the most common primary intracranial tumor and there is still no ideal treatment at present. Gene therapy, as one of the new methods for treating glioma, has attracted attention in recent years. But its application in treating glioma is very limited due to lack of effective delivery vectors. This study aims to investigate the feasibility of biomimetic nanomaterials made from glioma cells-derived extracellular vesicles (EV) for targeted delivery of signal transducers and activators of transcription 3 (STAT3)-small interfering RNA (siRNA) in treating glioma. METHODS: First, U251 glioma cells-derived extracellular vessel (EVU251) was extracted by ultra-centrifugal method. Nanoparticle tracking analysis was used to characterize the particle size distribution, the transmission electron microscope was used to analyze the morphology, and Western blotting was used to verify the expression of srface characteristic protein. The homing ability was verified by cell uptake assay after labeling EVU251 with membrane dye kit PKH67; the EVU251 contents were removed by a low permeability method and then EVMU251 was prepared through a microporous membrane. Finally, the biomimetic nanomaterials EVMU251@STAT3-siRNA were prepared by loading STAT3-SiRNA with electro-dyeing method. The real-time quantitative PCR was used to quantify the successful encapsulation of siRNA, and the encapsulation and drug loading rate was calculated; then Cy5-labeled siRNA was used to evaluate the ability of biomimetic nanomaterials (EVMU251@CY5-siRNA) to target U251 cells. Lysosomal escape ability of the biomimetic nanomaterial was evaluated by lysosomal dye lyso-tracker green. At last, the ability of EVMU251@STAT3-siRNA to knock down STAT3 gene and selective killing of U251 cells was detected by cell experiments in vitro. RESULTS: The size of EVU251 ranged from 50 nm to 200 nm with a natural disc shape. The expression of extracellular vesicle marker proteins could be detected on the membrane of EVU251. The cell uptake assay demonstrated that it had homing ability to target U251 cells. After EVU251 was prepared as EVMU251@STAT3-siRNA, the particle size was (177.9±5.0) nm, the siRNA loading rate was (33.5±2.2)% and the drug loading rate was (3.24±0.21)%. The biomimetic nanomaterial EVMU251@STAT3-siRNA still had the ability to target U251 cells and successfully deliver siRNA to the cytoplasm without lysosomal degradation. The EVMU251@STAT3-siRNA can effectively knock down the expression of STAT3 gene and produce selective killing ability in U251 cells. CONCLUSIONS The biomimetic nanomaterials EVMU251@STAT3-siRNA made from glioma U251 cells-derived extracellular vesicles can knock down STAT3 gene of U251 cells and produce selective killing effect, which can provide a new idea for the treatment of glioma.
Humans ; RNA, Small Interfering/genetics* ; Biomimetics ; Cell Line, Tumor ; Glioma/therapy* ; Nanostructures ; Cell Proliferation ; STAT3 Transcription Factor/metabolism*

OBJECTIVE: To show that Stat3 played a key role in the G1 to S phase transition in laryngocarcinoma cells. METHOD: Human laryngocarcinoma cell lines Hep-2 were transfected with Stat3 antisense oligonucleotide mediated by liposome, MTT assay was used to measure the proliferation, flow cytometry was applied to analyze the cell cycle, and the expressions of Stat3, phosphorylation specific Stat3 (tyrosine705), CyclinD1, Cyclin E, CDK2, CDK4, CDK6, p21 and p27 were detected by western blot. RESULT: Hep-2 laryngocarcinoma cell lines expressed constitutively activated Stat3. Antisense oligonucleotide which directed blocked up the translation site resulted in growth inhibition, downregulation of Stat3, p-Stat3, Cyclins and CDKs, and upregulation of p21 and p27. CONCLUSION Our findings suggested that Stat3 played an important role in the G1 to S phase transition in laryngocarcinoma cells, Stat3 orchestrated cell cycle by regulating the balance between CDK/Cyclin complex and CKI.
Cell Line, Tumor ; G1 Phase ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; S Phase ; STAT3 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; Transfection