ABSTRACT
The association of microRNA (miRNA) with tumor has gradually become an active medical research field, since its discovery in 1993. The aim of the present study was to clarify how microRNA16 expression affects the proliferation and survival of pituitary tumor, revealing its potential mechanism. MicroRNA16 expression of pituitary tumor patients was observably declined, compared with the normal group. A high expression of microRNA16 showed longer survival in pituitary tumor patients, compared to a low expression of microRNA16 in pituitary tumor patients. MicroRNA16 upregulation effectively decreased cell proliferation and induced apoptosis in HP75 cells. MicroRNA16 overexpression effectively induced p27, Bax protein expression and caspase3/8 activities, and suppressed phosphorylation-(p)-p38, NFκB, MMP9 and VEGFR2 protein expression in HP75 cells. After VEGFR2 suppression, the effects of microRNA16 overexpression on cell proliferation and apoptosis were significantly inhibited in HP75 cells. Moreover, the effects of microRNA16 overexpression on p27, Bax protein expression and caspase3/8 activities were significantly decreased in HP75 cells after p38 suppression. VEGFR2 or NFκB suppression reduced the effects of microRNA16 overexpression on pp38, NFκB, MMP9 and VEGFR2 protein expression inhibition in HP75 cells. Our results suggest that microRNA16 expression affects the proliferation and angiogenesis of pituitary cancer through the VEGFR2/p38/NFκB signaling pathway.
Subject(s)
MicroRNAs/metabolism , Pituitary Neoplasms/metabolism , Signal Transduction , Apoptosis , Caspases/metabolism , Cell Line, Tumor , Cell Proliferation , Humans , Matrix Metalloproteinase 9/metabolism , NF-kappa B/metabolism , Pituitary Neoplasms/enzymology , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Vascular Endothelial Growth Factor Receptor-2/metabolism , bcl-2-Associated X Protein/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
This study aimed to analyze the expression and clinical significance of cyclin G2 (CCNG2) in thyroid carcinoma and the biological effects of CCNG2 overexpression in a cell line. Immunohistochemistry and Western blotting were used to analyze CCNG2 protein expression in 63 cases of thyroid cancer and normal tissues to allow the relationship with clinical factors to be assessed. CCNG2 lentiviral and empty vectors were transfected into the thyroid cancer K1 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the mRNA and protein levels of CCNG2. MTT assay and cell cycle were also conducted to assess the influence of up-regulated expression of CCNG2 on K1 cell biology. The level of CCNG2 protein expression was found to be significantly lower in thyroid cancer tissue than normal tissues (P<0.05). Western blot: The relative amount of CCNG2 protein in thyroid cancer tissue was respectively found to be significantly lower than in normal tissues (P<0.05), correlating with lymph node metastasis, clinic stage and histological grade (P<0.05), but not gender, age or tumor size (P>0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time on Kaplan-Meier analysis (P<0.05). The results for biological functions showed that K1 cell transfected CCNG2 had a lower survival fraction, a greater percentage in the G0/G1 phases, and lower cyclin-dependent kinase 2 (CDK2) protein expression compared with K1 cells non-transfected with CCNG2 (P<0.05). CCNG2 expression decreased in thyroid cancer and correlated significantly lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator in thyroid cancer K1 cells by promoting degradation of CDK2.
