Analysis on gene profile of over-expression WWOX gene in human oral squamous cell carcinoma Tca8113 cells and tumor inhibition mechanism of WWOX gene / 吉林大学学报(医学版)

Objective: To analyze the changes of gene profile of over-expression WWOX gene in the human oral squamous cell carcinoma (OSCC) Tca8113 cells, and to explore the tumor inhibition mechanism of WWOX gene. Methods: The Tca8113 cells were divided into WWOX over-expression group and control group. In WWOX over-expression group, the lentiviral plasmid carrying the full-length cDNA fragment of WWOX gene was infected into the Tca8113 cells, while in control group, the lentiviral plasmid carrying the empty pGV287-LV vector was infected into the Tca8113 cells. The quantitative real time PCR (qRT-PCR) and Western blotting methods were used to detect the expressions of WWOX mRNA and protein. The gene chip technique was used to screen the differientially expressed genes and biological analysis was performed. The quantitative PCR was used to detect the relative mRNA expression levels of differientially expressed genes involving in the mitogen-activated protein kinase (MAPK) signaling pathway. Results: After infection, the relative mRNA expression level of WWOX gene in the Tca8113 cells in WWOX over-expression group was higher than that in control group (P<0. 05), and the expression of WWOX protein in the Tca8113 cells in WWOX over-expression group was higher. A total of 347 differientially expressed genes with a 1. 5-fold-change (FC) were screened by gene chip, in which 171 genes showed up-regulated expression, and 176 genes showed down-regulated expression. The Bioinformation analysis results showed that these different genes distributed in several pathways, which were related to cancer, p53, MAPK, and interleukin-2 (IL-2) pathways and so on. Compared with control group, the relative expression levels of MAP2K, NR4A1, DUSP5, and DUSP6 mRNA in MAPK signaling pathway in WWOX over-expression group were increased (P<0. 05), and the relative expression level of fibroblast growth factor receptor 2 (FGFR2) mRNA was decresed (P<0. 05). Conclusion: The over-expression of WWOX gene in the Tca8113 cells can induce the changes of gene profile of Tca8113 cells. The tumor inhibition mechanism of WWOX gene may be related to regulating the expressions of some genes involving in MAPK signaling pathway.

Expression of WWOX and C-JUN in keloid / 中华医学美学美容杂志

Objective To study the expression of WWOX and C-JUN in keloid and to approach their role and mechanism in the pathogenesis of keloid.Methods Immunohistochemical SP methods were used with computer pathological image analysis.Western blot and reverse transcription polymerase chain reaction (RT-RCR) were performed to detect the expression of WWOX and C-JUN in keloid and normal skin with statistical analysis.Results In keloid,the expression of WWOX protein was located in the cytoplasm of fibroblasts,and the expression of WWOX protein and its mRNA decreased,with significantly statistical difference (P＜0.05) compared to normal skin in the control group; the expression of C-JUN protein was located in the cell nucleus and cytoplasm of fibroblasts,with increased expression of C-JUN protein and its mRNA,with significantly statistical difference (P＜0.05) in comparison to normal skin in the control group.The expression of both was negative correlation (r=-0.626,P＜0.01).Conclusions Both WWOX with low expression and C-JUN with high expression are keloid-related genes,having significantly negative correlation between them,which may be one of the mechanisms for the keloid formation.It indicates that the WWOX protein may be an inhibitory factor to the expression of C-JUN protein,and the genes may play a major role in the pathogenesis of keloiod through fibroblasts.

Cloning of WWOX Gene and Its Growth-inhibiting Effects on Ovarian Cancer Cells / 华中科技大学学报（医学）（英德文版）

The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase (WWOX)gene on ovarian cancer cell line A2780 were investigated.The full length cDNA of human WWOX gene was amplified from normal human ovary tissues.The correct cDNA of full length WWOX was subcloned into eukaryocytic expression vector pCMV.After introduction of WWOX gene into cancer cells with liposome,the WWOX mRNA and protein level in the cancer cells were detected by reverse transcription polymerase chain reaction(RT-PCR)and immunoblotting.The growth activities of cancer cells were detected by Trypan blue staining.The clone formation assayin soft agar was employed to observe the proliferation of the cancer cells.Apoptosis was examined by DNA ladder and acridine orange-ethidium bromide fluorescent staining.The results showed that 72 h after WWOX gene transfection,the WWOX expression was increased significantly(P<0.01).The growth of ovarian cancer cells was decreased by 16.41% to 38.49%(P<0.01).The clone formation abilities were reduced(P<0.01).Some cancer cells presented the characteristic morphological changes of apoptosis with obvious ladder bands on electrophoresis.The apoptosis rate was(20.7±6.0)%(P<0.01).It was concluded that over-expression of WWOX gene could induce apoptosis and inhibit the growth of ovarian cancer cells,which might be potentially useful in the gene therapy of ovarian cancers.