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Zhao J.,Zhengzhou University | Zhao J.,Key Thoracic Tumour Experimental Laboratory of Zhengzhou | Qiao C.-R.,Zhengzhou University | Qiao C.-R.,Key Thoracic Tumour Experimental Laboratory of Zhengzhou | And 18 more authors.
Molecular Medicine Reports | Year: 2017

MicroRNAs (miRs) have emerged as being important in cancer biology. MIR-191 is a conserved miRNA, which has been investigated in detail and is reported to be induced by hypoxia-inducible factor (HIF)-1α and has an contributory action in the progression of breast, hepatic and pancreatic cancer. However, the effects of MIR-191 in the progression of lung cancer are a subject of debate. In the present study, it was found that the expression of MIR-191 was significantly upregulated in non-small cell lung cancer (NSCLC) cells in patients in vivo. However, the levels of MIR-191 remained unchanged in SK-MES-1, A549 and NCI-H460 NSCLC cell lines, compared with the level in the normal HBE lung cell line, however, the levels were markedly upregulated in these NSCLC cell lines under conditions of chronic hypoxia. Subsequently, an MIR-191 mimic was transfected into the NSCLC cell lines to examine its effect on the progression of the NSCLC cells in vitro. The data obtained using MTT and Cell counting kit-8 assays revealed that MIR-191 had no effect on the proliferation of the cells under normal condition, however, their proliferation was promoted under mild hypoxic conditions. In addition, the results of a Transwell migration assay showed that MIR-191 had a promoting effect on NSCLC cell migration under the conditions of chronic hypoxia. Furthermore, the TargetScan bioinformatics server and 3'-untranslated region luciferase reporter assay indicated that the transcription factor, nuclear factor 1α (NFIA) was a target of MIR-191. Subsequent western blot analysis showed that, in chronic-hypoxia, the protein levels of NFIA and the tumor suppressor, CCAAT-enhancer-binding protein α, were sharply reduced in A549 cells. In conclusion, MIR-191 was induced by chronic hypoxia and promoted the proliferation and migration of NSCLC cells under chronic hypoxic conditions. This promotion may be associated with its targeting of NFIA. The present findings may provide a potential molecular target for the therapeutic treatment of NSCLC.


Dang L.,Zhengzhou University | Wen F.,Zhengzhou University | Wen F.,Institute of Henan Province | Yang Y.,Zhengzhou University | And 13 more authors.
International Journal of Molecular Medicine | Year: 2014

Comprehensive treatment based on chemotherapy is regarded as the first-line treatment for patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, chemoresistance is common among patients with ESCC. Therefore, there is a need to explore new therapeutic strategies or adjuvant drugs. One promising possibility is to use dietary agents that can increase tumor cell sensitivity to drugs. In this study, we initially investigated the antitumor activity of proteasome inhibitor MG132 in vitro and in vivo. Effects of MG132 on the enhancment of the anticancer functions of cisplatin were then investigated in human esophageal cancer EC9706 cells in relation to apoptosis and cell signaling events. Exposure of cells to MG132 resulted in a marked decrease in cell viability in a dose- and time-dependent manner. Administration of MG132 markedly inhibited tumor growth in the EC9706 xenograft model. MG132 significantly enhanced cisplatin-induced apoptosis in association with the activation of caspase-3 and -8. These events were accompanied by the downregulation of NF-κB, which plays a key role in cell apoptosis. Taken together, these findings demonstrate a novel mechanism by which proteasome inhibitor MG132 potentiates cisplatin-induced apoptosis in human ESCC and inhibitory activity of tumor growth of the EC9706 xenograft model.


Zhao J.,Zhengzhou University | Zhao J.,Key Thoracic Tumour Experimental Laboratory of Zhengzhou | Li X.,Zhengzhou University | Li X.,Key Thoracic Tumour Experimental Laboratory of Zhengzhou | And 12 more authors.
OncoTargets and Therapy | Year: 2016

Background: YAP1, the nuclear effector of the Hippo pathway, has become an attractive target for treatment of malignancies and is a candidate oncogene in esophageal cancer (EC). We hypothesized that knockdown of YAP1 could suppress EC and could be used for targeted therapy. However, there are few reports of the effect of YAP1 knockdown in EC. Materials and methods: Quantitative real-time polymerase chain reaction and Western blot assays were performed to determine the expression levels of YAP1 mRNA and protein in primary EC tissue samples, EC cell lines, and controls. Immunohistochemistry was also performed to detect YAP1 protein expression in primary EC tumor and matched nontumor control tissues. YAP1-knockdown cell lines were constructed using short-hairpin RNA, and MTT, flow cytometry, and transwell chamber assays were used to analyze the effect of YAP1 knockdown on EC cell proliferation, apoptosis, and invasion. In vivo tumor formation assays were used to investigate the antitumor effect of YAP1 knockdown. Results: We found that YAP1 mRNA and protein were upregulated in EC and that YAP1 expression correlated significantly with metastasis and tumor stage. We also found that YAP1 knockdown repressed cell proliferation and invasion and promoted apoptosis of EC cell lines. In addition, animal experiments revealed that YAP1 knockdown suppressed the growth of esophageal tumors in vivo. Conclusion: Collectively, these data confirm our hypothesis that YAP1 knockdown suppresses EC and suggest that YAP1 knockdown could be exploited in the targeted gene therapy of EC in the future. © 2016 Zhao et al.

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