Effect of miRNA-200b on the proliferation of liver cancer cells via targeting SMYD2/p53 signaling pathway. / MiR-200b通过靶向调控SMYD2/p53信号通路抑制肝癌细胞增殖（英文）.

OBJECTIVES: Our previous study has verified that high level of SET and MYND domain-containing protein 2 (SMYD2) plays an important role in acquiring aggressive ability for liver cancer cells in hepatocellular carcinoma. MiR-200b as a tumor suppressor gene involves in a variety of cancers. This study aims to investigate the correlation between miR-200b and SMYD2 in hepatocellular carcinoma and the underlying mechanism. METHODS: Firstly, the levels of SMYD2 and miR-200b in hepatocellular carcinoma tissues and matched adjacent non-tumor liver tissues were tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Secondly, we evaluated the interaction between miR-200b and SMYD2 using dual-luciferase reporter assay. Thirdly, we elucidated the effect of miR-200b on SMYD2 and its downstream targets p53/CyclinE1. Finally, we silenced SMYD2 in hepatocellular carcinoma cell lines to investigate its effect on tumor proliferation and cell cycle progression, and further confirmed the correlation among SMYD2 and p53/CyclinE1. RESULTS: Compared with the matched adjacent non-tumor liver tissues, miR-200b was obviously decreased, and SMYD2 was significantly increased in hepatocellular carcinoma (both P<0.05). Spearman's rank correlation revealed that miR-200b expression was negatively correlated with SMYD2 (P<0.01). Computer algorithm and dual-luciferase reporter assay revealed that miR-200b directly targeted and suppressed SMYD2 in HEK 293T cells. The down-regulated miR-200b expression promoted hepatoma cell proliferation (P<0.05) and increased SMYD2 expression(P<0.01), while the up-regulated expression of miR-200b had an opposite effect. The knockdown of SMYD2 suppressed the proliferation of MHCC-97L cells (P<0.01), down-regulated CyclinE1, and up-regulated p53 expression (both P<0.05). CONCLUSIONS: MiR-200b is involved in hepatocellular carcinoma progression via targeting SMYD2 and regulating SMYD2/p53/CyclinE1 signaling pathway and may be used as a potential target for hepatocellular carcinoma treatment.

Roles of Cx43 and AKAP95 in ovarian cancer tissues in G1/S phase.

OBJECTIVE: The purpose of this study was to investigate the expression of A-kinase anchor protein 95 (AKAP95), cell cycle protein E1 (cyclinE1) and D1 (cyclinD1), and gap junction protein connexin 43 (Cx43) in ovarian cancer tissues, the relationship between four proteins and clinicopathologic parameters, and the correlation between these proteins. METHODS: The expression of proteins in 54 cases of ovarian cancer tissues was detected by immunohistochemical method. RESULTS: The positive expression rates of AKAP95, cyclinD1 and cyclinE1 in ovarian cancer tissues were 72.22%, 66.67% and 79.63%, respectively, which were higher than that of ovarian pericarcinoma tissues expressing as 33.33%, 25% and 8.30% (P<0.05). The positive expression rate of Cx43 in ovarian cancer tissues was 40.74%, which was lower than that of ovarian pericarcinoma tissues expressing as 75%; respectively, and the difference was statistically significant between groups (P<0.05). The expression of cyclinD1 in ovarian cancer tissues was related to the histologic type (P<0.05) while it showed no correlation with the degree of differentiation (P>0.05). Additionally, the expression of AKAP95, Cx43 and cyclinE1 in ovarian cancer tissues showed no correlation with the degree of differentiation or the histologic type (P>0.05). Protein expressions of AKAP95, Cx43 and cyclinE1 were correlated with each other (P<0.05), and the expressions of cyclinD1, cyclinE1 and Cx43 were also correlated with each other (P<0.05). However, AKAP95 and cyclinD1 showed no correlation (P>0.05). CONCLUSION: AKAP95, cyclinD1 and cyclinE1 play an important role in promoting the process of ovarian cancer formation. The tumor inhibitory effects of Cx43 protein on the pathogenesis of ovarian cancer were weakened. The expression of cyclinD1 in ovarian cancer tissues is related to the histologic type while it shows no correlation with the degree of differentiation. Additionally, the expression of AKAP95, Cx43 and cyclinE1 in ovarian cancer tissues shows no correlation with the degree of differentiation or the histologic type. AKAP95 expression is correlated with Cx43 and cyclinE1 expression; Cx43 expression is correlated with AKAP95, cyclinD1 and cyclinE1 expression; cyclinE1 expression is correlated with AKAP95, Cx43, cyclinD1 expression; cyclinD1 expression is correlated with Cx43 and cyclinE1 expression, while AKAP95 and cyclinD1 show no correlation.

Expression of AKAP95, Cx43, CyclinE1 and CyclinD1 in esophageal cancer and their association with the clinical and pathological parameters.

OBJECTIVE: To investigate correlations among A-kinase anchor protein95 (AKAP95), Connexin43 (Cx43), CyclinE1 and CyclinD1 in esophageal squamous cell cancer tissues, and their relationship with clinical and pathological parameters. METHODS: The protein levels of AKAP95, Cx43, CyclinE1 and CyclinD1 in 54 cases of esophageal squamous cell cancer tissues were determined by immunohistochemistry. RESULTS: The expression of AKAP95, CyclinE1 and CyclinD1 in esophageal squamous cell cancer tissues (53.70%, 88.89%, 72.22%, respectively) was significantly increased when compared to pericarcinoma tissues (20.00%, P < 0.05; 6.67%, P < 0.01; and 20.00%, P < 0.05; respectively). By contrast, Cx43 expression in esophageal squamous cell cancer tissues (22.22%) was lower than that in pericarcinoma tissues (60.00%, P < 0.05). The expression of AKAP95, Cx43, CyclinE1 and CyclinD1 in the tissues of esophageal squamous cell carcinoma was unrelated to lymph node metastasis and the degree of differentiation. The expression of Cx43, CyclinE1, CyclinD1 in the tissues of esophageal squamous cell carcinoma was significantly correlated with AKAP95, respectively (P < 0.05). CONCLUSION: Expression levels of AKAP95, CyclinE1 and CyclinD1 were higher, and that of Cx43 lower in esophageal squamous cell carcinoma tissues as compared pericarcinoma tissues, which suggests their importance in the incidence and development of esophageal squamous cell carcinoma. The expression of Cx43, CyclinE1, CyclinD1 in the tissues of esophageal squamous cell carcinoma was correlated with AKAP95, respectively. The expression of AKAP95, Cx43, CyclinE1 and CyclinD1 in the tissues of esophageal squamous cell carcinoma was unrelated to the degree of differentiation and lymph node metastasis.