Qicai Han1, Jie Yang2, Hao Yang1, Chao Li3, Juan Li4, Yuan Cao4. 1. Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 2. Department of Bone and Soft Tissue, Zhengzhou Central Affiliated Hospital to Zhengzhou University, Zhengzhou, China. 3. Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. 4. Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract
Background: Osteosarcoma (OS) is the most common primary bone malignancy, it has a dismal prognosis and mainly affects the children and adolescents. Previous reports have demonstrated that aberrantly expressed KIAA1429 plays crucial roles in the carcinogenesis of several cancers, but its expression status and functional role in the progression of OS have not previously been investigated. Methods: Immunohistochemistry (IHC) and western blotting were conducted to determine KIAA1429 expression status in OS. The relationship between KIAA1429 expression and OS prognosis was analyzed based on public database and tissue microarray (TMA). Cell proliferation ability was evaluated by CCK8, EdU and colony formation assays, and Transwell and wound healing potential were also assessed in vitro. Xenograft nude mouse model was performed to elucidate the tumor growth in vivo. The main specific miRNA targeting KIAA1429 in OS cells was identified. Results: KIAA1429 expression is markedly overexpressed in OS, and elevated KIAA1429 expression is significantly associated with an unfavorable prognosis. Functional investigations demonstrate that KIAA1429 silencing could attenuate proliferation, migration and invasion abilities of OS in vitro, as well as tumor growth in vivo. Mechanistically, microRNA-143-3p (miR-143-3p) was identified as the crucial specific mediator of KIAA1429 expression in OS cells. Furthermore, restoring KIAA1429 expression could partially reverse miR-143-3p mediated tumor-inhibition effects. Additionally, we found that knockdown of KIAA1429 or ectopic overexpression of miR-143-3p could repress stemness cell properties and the inhibition could be partly abolished by overexpression of KIAA1429.Conclusions: In summary, this study establishes miR-143-3p/KIAA1429 axis as promising therapeutic target for OS patients.
Background: Osteosarcoma (OS) is the most common primary bone malignancy, it has a dismal prognosis and mainly affects the children and adolescents. Previous reports have demonstrated that aberrantly expressed KIAA1429 plays crucial roles in the carcinogenesis of several cancers, but its expression status and functional role in the progression of OS have not previously been investigated. Methods: Immunohistochemistry (IHC) and western blotting were conducted to determine KIAA1429 expression status in OS. The relationship between KIAA1429 expression and OS prognosis was analyzed based on public database and tissue microarray (TMA). Cell proliferation ability was evaluated by CCK8, EdU and colony formation assays, and Transwell and wound healing potential were also assessed in vitro. Xenograft nude mouse model was performed to elucidate the tumor growth in vivo. The main specific miRNA targeting KIAA1429 in OS cells was identified. Results:KIAA1429 expression is markedly overexpressed in OS, and elevated KIAA1429 expression is significantly associated with an unfavorable prognosis. Functional investigations demonstrate that KIAA1429 silencing could attenuate proliferation, migration and invasion abilities of OS in vitro, as well as tumor growth in vivo. Mechanistically, microRNA-143-3p (miR-143-3p) was identified as the crucial specific mediator of KIAA1429 expression in OS cells. Furthermore, restoring KIAA1429 expression could partially reverse miR-143-3p mediated tumor-inhibition effects. Additionally, we found that knockdown of KIAA1429 or ectopic overexpression of miR-143-3p could repress stemness cell properties and the inhibition could be partly abolished by overexpression of KIAA1429.Conclusions: In summary, this study establishes miR-143-3p/KIAA1429 axis as promising therapeutic target for OS patients.
Authors: Philip Knuckles; Tina Lence; Irmgard U Haussmann; Dominik Jacob; Nastasja Kreim; Sarah H Carl; Irene Masiello; Tina Hares; Rodrigo Villaseñor; Daniel Hess; Miguel A Andrade-Navarro; Marco Biggiogera; Mark Helm; Matthias Soller; Marc Bühler; Jean-Yves Roignant Journal: Genes Dev Date: 2018-03-13 Impact factor: 11.361
Authors: Xinxin Peng; Zhongyuan Chen; Farshad Farshidfar; Xiaoyan Xu; Philip L Lorenzi; Yumeng Wang; Feixiong Cheng; Lin Tan; Kamalika Mojumdar; Di Du; Zhongqi Ge; Jun Li; George V Thomas; Kivanc Birsoy; Lingxiang Liu; Huiwen Zhang; Zhongming Zhao; Calena Marchand; John N Weinstein; Oliver F Bathe; Han Liang Journal: Cell Rep Date: 2018-04-03 Impact factor: 9.423