Xuanfu Xu1, Hua Liu, Hui Zhang, Weiqi Dai, Chuanyong Guo, Chuangao Xie, Shumei Wei, Shengli He, Xiaorong Xu. 1. From the *Department of Gastroenterology, The Tenth People's Hospital of Shanghai, Tongji University, Shanghai; Departments of †Pathology and ‡Gastroenterology, The Second Hospital of Zhejiang University, Hangzhou, Zhejiang Province; and §Department of Hepato-Biliary and Pancreatic Oncology, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, China.
Abstract
OBJECTIVES: The Hh (hedgehog) signaling pathway is still waiting for further studies because its downstream molecular mechanism remains elusive. Because EIF5A2 (eukaryotic translation initiation factor 5A2) gene was up-regulated upon Gli1 (GLI family zinc finger 1) in pancreatic cancer (PC) cells, we speculated that this pathway might promote tumor progression through regulating EIF5A2. METHODS: We investigated regulation effect of Hh signaling pathway to EIF5A2 gene transcription by Gli1 knockdown or overexpression in PC cell lines first. Then, the regulation mechanism of Gli1 to EIF5A2 gene was studied at transcription level. Finally, we studied cancer-promoting effects of Gli1-dependent EIF5A2 in PC cells. RESULTS: The data showed that Gli1 up-regulated expression of EIF5A2 by promoting transcription via cis-acting elements in PC cells. Moreover, vimentin gene was up-regulated significantly by sonic hedgehog (SHh)/Gli1 expression increasing, and E-cadherin was significantly reduced. The EIF5A2 knockdown partially reversed cell proliferation and migration induced by artificial SHh overexpression and inhibited epithelial mesenchymal transition process in PC cells with SHh overexpression (P < 0.05). CONCLUSIONS: Our data establish a novel transcription mechanism of Gli1 to EIF5A2 gene in cis-regulatory manner in PC cells. Thus, EIF5A2 oncogene effect could be incorporated into cancer-promoting molecular network upon Hh signaling pathway.
OBJECTIVES: The Hh (hedgehog) signaling pathway is still waiting for further studies because its downstream molecular mechanism remains elusive. Because EIF5A2 (eukaryotic translation initiation factor 5A2) gene was up-regulated upon Gli1 (GLI family zinc finger 1) in pancreatic cancer (PC) cells, we speculated that this pathway might promote tumor progression through regulating EIF5A2. METHODS: We investigated regulation effect of Hh signaling pathway to EIF5A2 gene transcription by Gli1 knockdown or overexpression in PC cell lines first. Then, the regulation mechanism of Gli1 to EIF5A2 gene was studied at transcription level. Finally, we studied cancer-promoting effects of Gli1-dependent EIF5A2 in PC cells. RESULTS: The data showed that Gli1 up-regulated expression of EIF5A2 by promoting transcription via cis-acting elements in PC cells. Moreover, vimentin gene was up-regulated significantly by sonic hedgehog (SHh)/Gli1 expression increasing, and E-cadherin was significantly reduced. The EIF5A2 knockdown partially reversed cell proliferation and migration induced by artificial SHh overexpression and inhibited epithelial mesenchymal transition process in PC cells with SHh overexpression (P < 0.05). CONCLUSIONS: Our data establish a novel transcription mechanism of Gli1 to EIF5A2 gene in cis-regulatory manner in PC cells. Thus, EIF5A2 oncogene effect could be incorporated into cancer-promoting molecular network upon Hh signaling pathway.
Authors: Yekaterina Galat; Haigang Gu; Mariana Perepitchka; Robert Taylor; Joon Won Yoon; Xenia A Glukhova; Xiao-Nan Li; Igor P Beletsky; David O Walterhouse; Vasiliy Galat; Philip M Iannaccone Journal: Stem Cells Date: 2021-02-22 Impact factor: 6.277
Authors: Robert Taylor; Jun Long; Joon Won Yoon; Ronnie Childs; Kathrine B Sylvestersen; Michael L Nielsen; King-Fu Leong; Stephen Iannaccone; David O Walterhouse; David J Robbins; Philip Iannaccone Journal: DNA Repair (Amst) Date: 2019-05-02