2.Expression of MUC15 and PI3K/Akt in gastric carcinoma and its association with clini-copathological characteristics and prognosis
Zhiwei HAN ; Ruizhou RONG ; Pengzhou KONG ; Caixia CHENG ; Yanyan ZHANG ; Jinyao DONG ; Shujing LI ; Jiansheng GUO
Chinese Journal of Clinical Oncology 2016;(2):56-61
Objective:To analyze the expression of MUC15 and PI3K/Akt in gastric carcinoma and its association with clinicopathologi-cal characteristics and prognosis. Methods:The expression of MUC15 and Akt was detected in 144 cases of gastric carcinoma tissues and corresponding para-carcinoma tissues by tissue microarray and immunohistochemistry. Results:The positive expression rate of MUC15 in gastric carcinoma was 79.8%, higher than that of para-carcinoma tissues (22.2%, P<0.01). The positive expression rate of Akt protein in gastric carcinoma was 80.6%, higher than that of para-carcinoma tissues (16.7%, P<0.01). The expression of MUC15 and Akt was statistically associated with the grades of differentiation, invasion depth, lymphatic metastasis, TNM stage of tumor tissues (P<0.05), and the positive correlation between the two protein expression that appear in the gastric tumor tissue (P=0.001). Univariate survival analysis showed that the over-expression of either MUC15 or Akt was inversely correlated with the survival time (P<0.05 and P<0.01, respectively). Cox multiple regression analysis indicated that patients with over-expression of both MUC15 and Akt had the worst prognoses (HR=3.115, P<0.05). Conclusion:MUC15 may be involved in the occurrence, development, invasion, and metastasis of gastric cancer through the PI3K/Akt cell signaling pathway, and the expression of MUC15 combined with Akt is a powerful predictor for the prognosis of gastric cancer.
3.Effect of puerarin on proliferation and apoptosis of human gastric cancer MGC-803 and AGS cells
Xiaole MA ; Yixia YU ; Yu ZHANG ; Jinyao DONG ; Zhijie DU ; Jiansheng GUO
Cancer Research and Clinic 2013;25(9):585-587
Objective To study the effects of puerarin on proliferation and apoptosis of human gastric cancer MGC-803 and AGS cells.Methods Human gastric cancer cells were treated with puerarin at different concentrations.MTT assay was used to test cell proliferation and FCM was used to detect cell apoptosis.Results The inhibition rates had upwarded trend with increasing concentrations (MGC-803:1.24 %,2.80 %,15.10 %,18.55 %,59.65 %; AGS:15.59 %,25.31%,30.25 %,36.91%,64.47 %),when treated with puerarin at different concentrations (1.5,3.0,6.0 12.0,24.0 mmol/L) for 48 hours.Apoptosis rates gradually increased with increasing concentrations (MGC-803:5.49 %,9.53 %,13.81%; AGS:6.23 %,16.38 %,25.99 %),when treated with puerarin at different concentrations (0,12.0,24.0 mmol/L) for 24 hours.Conclusion Puerarin inhibits proliferation and induces apoptosis of human gastric cancer cells MGC-803 and AGS.
4.Expression and correlation of phosphorylation extracellular signal-regulated kinase and monopolar spindle 1 in colorectal cancer with wild type or BRAF V600E mutation
Jing LIU ; Jinyao DONG ; Yanyan ZHANG ; Zhigang WEI ; He HUANG ; Jiansheng GUO
Cancer Research and Clinic 2018;30(4):222-228
Objective To determine the correlation between phosphorylation extracellular signal-regulated kinase (p-Erk) and monopolar spindle 1 (Mps1) in colorectal cancer patients with the BRAF V600E mutation or not, and to explore the relationship between the expression of p-Erk and Mps1 with the clinicopathological features and prognosis of colorectal cancer patients. Methods Two hundred and eighty-eight paraffin-embedded tissue sections containing both the carcinoma and its adjacent non-neoplastic colorectal tissue were collected from January 2009 to June 2015 in the First Hospital of Shanxi Medical University. BRAF mutation was detected by Sanger sequencing. Kaplan-Meier survival analysis was used to analyze the correlation between BRAF V600E and prognosis. Immunohistochemistry was used to detect the expression level of p-Erk and Mps1 in colorectal cancer with wild type or BRAF V600E mutation. The correlation between p-ERK and Mps1 expression was analyzed by using linear regression analysis. Results The BRAF V600E mutation rate was 5.2 % in colorectal carcinomas. In addition, the poorly differentiated tumours and mucinous tumours had higher incidence of BRAF mutations than well differentiated tumours and non-mucinous tumours respectively [14.3 % (9/63) vs. 2.7 % (6/225),χ 2= 11.208,P = 0.001; 25.0 % (6/24) vs. 3.4 %(9/264),χ 2=16.630,P <0.001). The positive rate of p-Erk and Mps1 in colorectal carcinomas with BRAF V600E was significantly higher than that in colorectal carcinomas with BRAF WT (14/15 vs. 3/15, P <0.05; 15/15 vs. 3/15, P < 0.05]. It was found that the p-Erk expression correlated positively to the Mps1 expression (R2= 0.419,P < 0.001). The expressions of p-Erk protein in poorly differentiated adenocarcinoma was significantly higher and mucinous adenocarcinoma than those in high differentiated adenocarcinoma and non-mucinous adenocarcinoma (χ 2= 6.679, P = 0.01; χ 2= 5.735, P = 0.017), as well as in the group with lymph node metastasis than without lymph node metastasis (χ 2=5.436, P =0.02). Positive rate of Mps1 in poorly differentiated carcinoma was higher than that in well differentiated adenocarcinoma of colorectal carcinomas (χ 2=7.950, P =0.009). The Kaplan-Meier survival analysis indicated that patients with BRAF V600E had a worse survival rate than BRAF WT patients. Conclusions BRAF V600E may play an important role in specific pathological kinds of colorectal carcinomas, which is expected to be an independent prognostic factor. The expression of p-Erk is significantly correlated with Mps1 in colorectal carcinomas, suggesting that Mps1 may become a new potential target for targeted therapy.
5.BRAF-Activated Long Noncoding RNA Modulates Papillary Thyroid Carcinoma Cell Proliferation through Regulating Thyroid Stimulating Hormone Receptor.
Haitao ZHENG ; Meng WANG ; Lixin JIANG ; Haidi CHU ; Jinchen HU ; Jinyao NING ; Baoyuan LI ; Dong WANG ; Jie XU
Cancer Research and Treatment 2016;48(2):698-707
PURPOSE: The importance of long noncoding RNAs (lncRNAs) in tumorigenesis has recently been demonstrated. However, the role of lncRNAs in development of thyroid cancer remains largely unknown. MATERIALS AND METHODS: Using quantitative reverse transcription polymerase chain reaction, expression of three lncRNAs, including BRAF-activated long noncoding RNA (BANCR), papillary thyroid cancer susceptibility candidate 3 (PTCSC3), and noncoding RNA associated with mitogen-activated protein kinase pathway and growth arrest (NAMA), was investigated in the current study. RESULTS: Of the three lncRNAs (BANCR, PTCSC3, and NAMA), expression of BANCR was significantly up-regulated while PTCSC3 and NAMA were significantly down-regulated in papillary thyroid carcinoma (PTC) compared to that in normal tissue. BANCR-knockdown in a PTC-derived cell line (IHH-4) resulted in significant suppression of thyroid stimulating hormone receptor (TSHR). BANCR-knockdown also led to inhibition of cell growth and cell cycle arrest at G0/G1 phase through down-regulation of cyclin D1. In addition, BANCR was enriched by polycomb enhancer of zeste homolog 2 (EZH2), and silencing BANCR led to decreased chromatin recruitment of EZH2, which resulted significantly reduced expression of TSHR. CONCLUSION: These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.
Carcinogenesis
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Cell Cycle Checkpoints
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Cell Line
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Cell Proliferation*
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Chromatin
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Cyclin D1
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Down-Regulation
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Polymerase Chain Reaction
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Protein Kinases
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Receptors, Thyrotropin*
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Reverse Transcription
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RNA, Long Noncoding*
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RNA, Untranslated
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Thyroid Gland*
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Thyroid Neoplasms*
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Thyrotropin*