Yulei Gu1,2, Chao Li3, Lili Xiao1, Juan Li1, Hui Pei1, Dong Xu1, Yumin Jiang1, Xiaofan Zhang1, Luanluan Zhang1, Kongfei Li4, Zhiqiang Zhu2, Xiaolong Chen1. 1. Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China. 2. Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China. 3. Department of Orthopaedic Surgery, The Affiliated Cancer Hospital of Zhengzhou University 127 Dongming Road, Zhengzhou 450008, Henan Province, China. 4. Department of Hematology, Yinzhou People's Hospital Affiliated to Medical College of Ningbo University Ningbo, Zhejiang Province, China.
Abstract
BACKGROUND: Cholangiocarcinoma (CCA) is a biliary malignancy, which is notoriously difficult to diagnose and associated with poor survival. Accumulating evidence indicates that long non-coding RNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) is overexpressed in several tumors and plays a crucial role in the development of neoplasm. However, the expression pattern and functional role of NNT-AS1 in CCA remain largely unknown. METHODS: NNT-AS1 expression was assessed by RT-qPCR and In Situ Hybridization (ISH) assay. The clinical relevance of NNT-AS1 was analyzed using a CCA tissue microarray with follow-up data. The function role of NNT-AS1 and its underlying molecular mechanisms were evaluated using both in vitro/in vivo experiments and bioinformatics analysis. Luciferase reporter assay, western blot and RT-qPCR were conducted to identify the miRNA/target gene involved in the regulation of CCA progression. RESULTS: LncRNA NNT-AS1 was found highly expressed in CCA. Upregulated NNT-AS1 expression was tightly associated with clinical malignancies and predicted poor prognosis of CCA patients. Functional studies showed that NNT-AS1 knockdown inhibited cell proliferation, migration and invasion of CCA cells in vitro. Conversely, NNT-AS1 overexpression showed the opposite biological effects. In a tumor xenograft model, we confirmed that NNT-AS1 knockdown could significantly inhibit the growth of CCA, while NNT-AS1 overexpression promoted CCA development. Mechanistically, we demonstrated that NNT-AS1 might function as a ceRNA in regulating HMGA2 (high mobility group AT-hook 2) through competitively binding to miR-142-5p in CCA. Moreover, we showed that NNT-AS1 regulated epithelial-mesenchymal transition in CCA. CONCLUSION: In summary, these findings suggest the potential prognostic and therapeutic value of NNT-AS1/miR-142-5p/HMGA2 axis in CCA patients. AJTR
BACKGROUND:Cholangiocarcinoma (CCA) is a biliary malignancy, which is notoriously difficult to diagnose and associated with poor survival. Accumulating evidence indicates that long non-coding RNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) is overexpressed in several tumors and plays a crucial role in the development of neoplasm. However, the expression pattern and functional role of NNT-AS1 in CCA remain largely unknown. METHODS:NNT-AS1 expression was assessed by RT-qPCR and In Situ Hybridization (ISH) assay. The clinical relevance of NNT-AS1 was analyzed using a CCA tissue microarray with follow-up data. The function role of NNT-AS1 and its underlying molecular mechanisms were evaluated using both in vitro/in vivo experiments and bioinformatics analysis. Luciferase reporter assay, western blot and RT-qPCR were conducted to identify the miRNA/target gene involved in the regulation of CCA progression. RESULTS: LncRNA NNT-AS1 was found highly expressed in CCA. Upregulated NNT-AS1 expression was tightly associated with clinical malignancies and predicted poor prognosis of CCApatients. Functional studies showed that NNT-AS1 knockdown inhibited cell proliferation, migration and invasion of CCA cells in vitro. Conversely, NNT-AS1 overexpression showed the opposite biological effects. In a tumor xenograft model, we confirmed that NNT-AS1 knockdown could significantly inhibit the growth of CCA, while NNT-AS1 overexpression promoted CCA development. Mechanistically, we demonstrated that NNT-AS1 might function as a ceRNA in regulating HMGA2 (high mobility group AT-hook 2) through competitively binding to miR-142-5p in CCA. Moreover, we showed that NNT-AS1 regulated epithelial-mesenchymal transition in CCA. CONCLUSION: In summary, these findings suggest the potential prognostic and therapeutic value of NNT-AS1/miR-142-5p/HMGA2 axis in CCApatients. AJTR
Authors: Steven R Alberts; Gregory J Gores; George P Kim; Lewis R Roberts; Michael L Kendrick; Charles B Rosen; Suresh T Chari; James A Martenson Journal: Mayo Clin Proc Date: 2007-05 Impact factor: 7.616
Authors: Sarah Djebali; Carrie A Davis; Angelika Merkel; Alex Dobin; Timo Lassmann; Ali Mortazavi; Andrea Tanzer; Julien Lagarde; Wei Lin; Felix Schlesinger; Chenghai Xue; Georgi K Marinov; Jainab Khatun; Brian A Williams; Chris Zaleski; Joel Rozowsky; Maik Röder; Felix Kokocinski; Rehab F Abdelhamid; Tyler Alioto; Igor Antoshechkin; Michael T Baer; Nadav S Bar; Philippe Batut; Kimberly Bell; Ian Bell; Sudipto Chakrabortty; Xian Chen; Jacqueline Chrast; Joao Curado; Thomas Derrien; Jorg Drenkow; Erica Dumais; Jacqueline Dumais; Radha Duttagupta; Emilie Falconnet; Meagan Fastuca; Kata Fejes-Toth; Pedro Ferreira; Sylvain Foissac; Melissa J Fullwood; Hui Gao; David Gonzalez; Assaf Gordon; Harsha Gunawardena; Cedric Howald; Sonali Jha; Rory Johnson; Philipp Kapranov; Brandon King; Colin Kingswood; Oscar J Luo; Eddie Park; Kimberly Persaud; Jonathan B Preall; Paolo Ribeca; Brian Risk; Daniel Robyr; Michael Sammeth; Lorian Schaffer; Lei-Hoon See; Atif Shahab; Jorgen Skancke; Ana Maria Suzuki; Hazuki Takahashi; Hagen Tilgner; Diane Trout; Nathalie Walters; Huaien Wang; John Wrobel; Yanbao Yu; Xiaoan Ruan; Yoshihide Hayashizaki; Jennifer Harrow; Mark Gerstein; Tim Hubbard; Alexandre Reymond; Stylianos E Antonarakis; Gregory Hannon; Morgan C Giddings; Yijun Ruan; Barbara Wold; Piero Carninci; Roderic Guigó; Thomas R Gingeras Journal: Nature Date: 2012-09-06 Impact factor: 49.962