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Nie J.,Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection | Nie J.,The Interdisciplinary Center | Nie J.,Soochow University of China | Ge X.,Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection | And 13 more authors.
Oncology Reports | Year: 2015

Esophageal squamous cell carcinoma (ESCC), one of the most common gastrointestinal tumors, is known for its high mortality rate. microRNAs (miRNAs) have been reported to play important regulatory roles in cancer metastasis and progression. miR-34a has been demonstrated to be associated with the development of and metastasis in certain types of cancer via various target genes, but its function and targets in ESCC are unknown. The aim of this study was to examine whether the expression of miR-34a was significantly decreased in ESCC tissues, compared with normal esophageal tissues using RT-PCR and western blot analysis. The results showed that miR-34a overexpression increased apoptosis and decreased clonogenic formation, but inhibited invasion and migration in ESCC cells by suppressing MMP-2 and -9 expression. Yin Yang-1 (YY1), a widely distributed transcription factor that belongs to the GLI-Kruppel class of zinc finger proteins, was found to be a direct target of miR-34a in ESCC cell lines. Rescue experiments indicated that the suppressive effect of miR-34a on invasion and migration was mediated by activating YY1 expression. Results of the present study showed that miR-34a is associated with ESCC migration and provides a potential therapeutic and diagnostic target for ESCC. © 2015, Spandidos Publications. All rights reserved. Source


Zhu W.,Soochow University of China | Liu J.,Soochow University of China | Nie J.,Soochow University of China | Sheng W.,Soochow University of China | And 7 more authors.
Oncology Reports | Year: 2015

Radiotherapy is a common treatment modality for lung cancer, however, radioresistance remains a fundamental barrier to attaining the maximal efficacy. Cancer cells take advantage of the ubiquitin-proteasome system (UPS) for increased proliferation and decreased apoptotic cell death. MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal-H), a specific and selective reversible inhibitor of the 26S proteasome, has shown anticancer effect in multiple types of cancers. Previously, we have reported that MG132 enhances the anti-growth and anti-metastatic effects of irradiation in lung cancer cells. However, whether MG132 can enhance the radiosensitivity in lung cancer cells in vitro and in vivo is still unknown. In this study, we found that MG132 increased apoptosis and dicentric chromosome ratio of A549 and H1299 cells treated by irradiation. Radiation-induced NF-κB expression and IκBα phosphorylation was attenuated in MG132 plus irradiation- treated cells. The in vivo model of H1299 xenografts of nude mice showed that the tumor size of MG132 plus irradiation treated xenografts was smaller than that of irradiation, MG132 or the control group. Moreover, MG132 plus irradiation group showed significant reduced Ki67 expression. Taken together, these results demonstrate that MG132 enhances the radiosensitivity through multiple mechanisms in vitro and in vivo. Source


Liu P.,Affiliated Jiangyin Hospital of Southeast University | Gao Y.,Affiliated Jiangyin Hospital of Southeast University | Huan J.,Soochow University of China | Ge X.,Soochow University of China | And 7 more authors.
Cellular Physiology and Biochemistry | Year: 2015

Background/Aims: This study investigated the clinical relevance and biological function of paired box gene 2 (PAX2) in esophageal squamous cell carcinoma (ESCC). Methods/Results: Results showed that PAX2 expression was significantly increased in tumor tissues and that its expression correlated with the ESCC stage (P = 0.001), lymph node metastasis (pN, P = 0.019) and lymphatic invasion (P = 0.005) in 120 ESCC tissue specimens by immunohistochemistry. Furthermore, PAX2 overexpression resulted in markedly reduced cell proliferation but increased metastasis capacity in ESCC TE-1 and Eca-109 cells. Knockdown of PAX2 expression with a short hairpin RNA confirmed a role in the promotion of metastasis in ESCC cells. mRNA microarray screening revealed that PAX2 overexpression affected multiple genes that function in multiple pathways. Interleukin-5 (IL-5), which was induced by PAX2 and has been shown to promote tumor metastasis, was further studied in greater detail. Two PAX2 binding sites were identified in the IL-5 promoter, and PAX2 was observed to stimulate IL-5 promoter activity and IL-5 expression in esophageal cancer cells. Chromatin immunoprecipitation (ChIP) confirmed the direct binding of PAX2 in the IL-5 promoter. The expression of PAX2 mRNA significantly correlated with that of IL-5 in normal esophageal and ESCC tissues. Conclusion: These findings demonstrate that PAX2 is overexpressed in esophageal carcinoma and IL-5 is identified as PAX2's effector for metastasis. © 2015 S. Karger AG, Basel. Source

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