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Role of MetallothioneinlH in Cisplatin Resistance of Non-Small Cell Lung Cancer Cells 被引量:1
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作者 Xin-fang Hou Qing-xia Fan +1 位作者 liu-xing wang Shi-xin LU 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2009年第4期247-254,共8页
Objective: Despite platinum-based adjuvant chemotherapy has improved greatly patients' outcomes, drug resistance poses a major impediment to the successful use of such an effective agent. Metallothioneins(MTs) are... Objective: Despite platinum-based adjuvant chemotherapy has improved greatly patients' outcomes, drug resistance poses a major impediment to the successful use of such an effective agent. Metallothioneins(MTs) are known to play putative roles in cancer cell proliferation, apoptosis, differentiation, drug resistance and prognosis. The present studiy was to investigte the role of metallethioeinlH(MTIH) in cisplatin resistance of human non-small cell lung cancer(NSCLC) cell lines in vitro or its possible molecular mechanisms. Methods: MTIH mRNA expression in A549 and A549/DDP cells was detected by RT-PCR. A recombinant eukaryotic expression plasmid pcDNA3.1(-)-MT1H was constructed and transfected into A549 cells which express no MTIH. MT1H siRNA was transfected into A549/DDP cells which express MTIH highly. MTIH expression was detected by RT-PCR and Immunoblot. The chemosensitivity to cisplatin was assessed by MTT assay. Apoptosis rate was determined by Tunel and FCM. Bcl-2 and Bax were determined by immunohistochemistry. Results: MT1H mRNA was expressed in A549/DDP but not in A549. After transfection of MT1H, MT1H expression was enhanced and the chemosensitivity to cisplatin was decreased in A549 cells. Inversely, after transfection of MT1H siRNA, MT1H expression was decreased and the chemosensitivity to cisplatin was increased in A549/DDP. The apoptosis rate induced by cisplatin was increased and Bcl-2 was down-regulated but Bax showed little change in A549/DDP cells interferred with MT1H siRNA. Conclusion: MT1H overexpression can promote drug resistance in A549 cells . Down-regulation of MTIH interfered with siRNA can effectively reverses the drug resistance in A549/DDP cells by down-regulating the expression of Bcl-2 and increasing cisplatin induced apoptosis. SiRNA targeting MT1H combined with chemotherapy may be a very promising strategy for treatment of lung cancer. 展开更多
关键词 METALLOTHIONEIN MT1H Non-small-cell lung cancer Drug resistance APOPTOSIS
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Analysis of cyclin E co-expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer 被引量:2
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作者 Liang-Yu Bie Dan Li +15 位作者 Yu Mu Sheng wang Bei-Bei Chen Hui-Fang Lyu Li-Li Han Cai-Yun Nie Chang-Cheng Yang Lin wang Chuan-Chuan Ren Wei-Jie Zhang Ping Guo Feng Shi Qing-Xia Fan liu-xing wang Xiao-Bing Chen Su-Xia Luo 《Chronic Diseases and Translational Medicine》 CSCD 2019年第1期44-52,共9页
Objective: To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. Methods: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencin... Objective: To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. Methods: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan-Meier survival curve analysis. Results: After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors’ clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05). Conclusions: NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer. 展开更多
关键词 Cyclin E NUCLEAR transcription factor Y SUBUNIT alpha ONCOGENE Gastric cancer
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