JiaLing Chen1, Bin Du2. 1. Department of Pathology, School of Medicine, Jinan University, Guangzhou, China. 2. Department of Pathology, School of Medicine, Jinan University, Guangzhou, China. tdubin@jnu.edu.cn.
Abstract
PURPOSE: The fat mass- and obesity-associated (FTO) gene on chromosome 16q12.2 shows an intimate association with obesity and body mass index. Recently, research into the FTO gene and its expression product has attracted widespread interest due to the identification of FTO as an N6-methyladenosine (m6A) demethylase. FTO primarily regulates the m6A levels of downstream targets via their 3' untranslated regions. FTO not only plays a critical role in obesity-related diseases but also is involved in the occurrence, development and prognosis of many types of cancer, such as acute myeloid leukaemia, glioblastoma and breast cancer. Currently, studies indicate that FTO is a crucial component of m6A modification, it regulates cancer stem cell function, and promotes the growth, self-renewal and metastasis of cancer cells. In this review, we summarized and analysed the data regarding the structural features and biological functions of FTO as well as its association with different cancers and possible molecular mechanisms. METHODS: We systematically reviewed the related literatures regarding FTO and its demethylation activity in many pathologic and physiological processes, especially in cancer-related diseases based on PubMed databases in this article. RESULTS: Mounting evidence indicated that FTO plays a critical role in occurrence, progression and treatment of various cancers, even acting as a cancer oncogene in acute myeloid leukaemia, research on which is no longer restricted to metabolic diseases such as obesity and diabetes. CONCLUSION: Considering FTO's critical role in many diseases, FTO may become a new promising target for the diagnosis and treatment of various diseases in the near future, especially for specific types of cancers, such as acute myeloid leukaemia, glioblastoma and breast cancer.
PURPOSE: The fat mass- and obesity-associated (FTO) gene on chromosome 16q12.2 shows an intimate association with obesity and body mass index. Recently, research into the FTO gene and its expression product has attracted widespread interest due to the identification of FTO as an N6-methyladenosine (m6A) demethylase. FTO primarily regulates the m6A levels of downstream targets via their 3' untranslated regions. FTO not only plays a critical role in obesity-related diseases but also is involved in the occurrence, development and prognosis of many types of cancer, such as acute myeloid leukaemia, glioblastoma and breast cancer. Currently, studies indicate that FTO is a crucial component of m6A modification, it regulates cancer stem cell function, and promotes the growth, self-renewal and metastasis of cancer cells. In this review, we summarized and analysed the data regarding the structural features and biological functions of FTO as well as its association with different cancers and possible molecular mechanisms. METHODS: We systematically reviewed the related literatures regarding FTO and its demethylation activity in many pathologic and physiological processes, especially in cancer-related diseases based on PubMed databases in this article. RESULTS: Mounting evidence indicated that FTO plays a critical role in occurrence, progression and treatment of various cancers, even acting as a cancer oncogene in acute myeloid leukaemia, research on which is no longer restricted to metabolic diseases such as obesity and diabetes. CONCLUSION: Considering FTO's critical role in many diseases, FTO may become a new promising target for the diagnosis and treatment of various diseases in the near future, especially for specific types of cancers, such as acute myeloid leukaemia, glioblastoma and breast cancer.
Authors: Irene P Tzanetakou; Nikolaos L Katsilambros; Athanase Benetos; Dimitrios P Mikhailidis; Despina N Perrea Journal: Ageing Res Rev Date: 2011-12-13 Impact factor: 10.895
Authors: Shideng Bao; Qiulian Wu; Roger E McLendon; Yueling Hao; Qing Shi; Anita B Hjelmeland; Mark W Dewhirst; Darell D Bigner; Jeremy N Rich Journal: Nature Date: 2006-10-18 Impact factor: 49.962
Authors: Steven Robbens; Pierre Rouzé; J Mark Cock; Jürg Spring; Alexandra Z Worden; Yves Van de Peer Journal: J Mol Evol Date: 2007-12-04 Impact factor: 2.395
Authors: Montserrat Garcia-Closas; Fergus J Couch; Sara Lindstrom; Kyriaki Michailidou; Marjanka K Schmidt; Mark N Brook; Nick Orr; Suhn Kyong Rhie; Elio Riboli; Heather S Feigelson; Loic Le Marchand; Julie E Buring; Diana Eccles; Penelope Miron; Peter A Fasching; Hiltrud Brauch; Jenny Chang-Claude; Jane Carpenter; Andrew K Godwin; Heli Nevanlinna; Graham G Giles; Angela Cox; John L Hopper; Manjeet K Bolla; Qin Wang; Joe Dennis; Ed Dicks; Will J Howat; Nils Schoof; Stig E Bojesen; Diether Lambrechts; Annegien Broeks; Irene L Andrulis; Pascal Guénel; Barbara Burwinkel; Elinor J Sawyer; Antoinette Hollestelle; Olivia Fletcher; Robert Winqvist; Hermann Brenner; Arto Mannermaa; Ute Hamann; Alfons Meindl; Annika Lindblom; Wei Zheng; Peter Devillee; Mark S Goldberg; Jan Lubinski; Vessela Kristensen; Anthony Swerdlow; Hoda Anton-Culver; Thilo Dörk; Kenneth Muir; Keitaro Matsuo; Anna H Wu; Paolo Radice; Soo Hwang Teo; Xiao-Ou Shu; William Blot; Daehee Kang; Mikael Hartman; Suleeporn Sangrajrang; Chen-Yang Shen; Melissa C Southey; Daniel J Park; Fleur Hammet; Jennifer Stone; Laura J Van't Veer; Emiel J Rutgers; Artitaya Lophatananon; Sarah Stewart-Brown; Pornthep Siriwanarangsan; Julian Peto; Michael G Schrauder; Arif B Ekici; Matthias W Beckmann; Isabel Dos Santos Silva; Nichola Johnson; Helen Warren; Ian Tomlinson; Michael J Kerin; Nicola Miller; Federick Marme; Andreas Schneeweiss; Christof Sohn; Therese Truong; Pierre Laurent-Puig; Pierre Kerbrat; Børge G Nordestgaard; Sune F Nielsen; Henrik Flyger; Roger L Milne; Jose Ignacio Arias Perez; Primitiva Menéndez; Heiko Müller; Volker Arndt; Christa Stegmaier; Peter Lichtner; Magdalena Lochmann; Christina Justenhoven; Yon-Dschun Ko; Taru A Muranen; Kristiina Aittomäki; Carl Blomqvist; Dario Greco; Tuomas Heikkinen; Hidemi Ito; Hiroji Iwata; Yasushi Yatabe; Natalia N Antonenkova; Sara Margolin; Vesa Kataja; Veli-Matti Kosma; Jaana M Hartikainen; Rosemary Balleine; Chiu-Chen Tseng; David Van Den Berg; Daniel O Stram; Patrick Neven; Anne-Sophie Dieudonné; Karin Leunen; Anja Rudolph; Stefan Nickels; Dieter Flesch-Janys; Paolo Peterlongo; Bernard Peissel; Loris Bernard; Janet E Olson; Xianshu Wang; Kristen Stevens; Gianluca Severi; Laura Baglietto; Catriona McLean; Gerhard A Coetzee; Ye Feng; Brian E Henderson; Fredrick Schumacher; Natalia V Bogdanova; France Labrèche; Martine Dumont; Cheng Har Yip; Nur Aishah Mohd Taib; Ching-Yu Cheng; Martha Shrubsole; Jirong Long; Katri Pylkäs; Arja Jukkola-Vuorinen; Saila Kauppila; Julia A Knight; Gord Glendon; Anna Marie Mulligan; Robertus A E M Tollenaar; Caroline M Seynaeve; Mieke Kriege; Maartje J Hooning; Ans M W van den Ouweland; Carolien H M van Deurzen; Wei Lu; Yu-Tang Gao; Hui Cai; Sabapathy P Balasubramanian; Simon S Cross; Malcolm W R Reed; Lisa Signorello; Qiuyin Cai; Mitul Shah; Hui Miao; Ching Wan Chan; Kee Seng Chia; Anna Jakubowska; Katarzyna Jaworska; Katarzyna Durda; Chia-Ni Hsiung; Pei-Ei Wu; Jyh-Cherng Yu; Alan Ashworth; Michael Jones; Daniel C Tessier; Anna González-Neira; Guillermo Pita; M Rosario Alonso; Daniel Vincent; Francois Bacot; Christine B Ambrosone; Elisa V Bandera; Esther M John; Gary K Chen; Jennifer J Hu; Jorge L Rodriguez-Gil; Leslie Bernstein; Michael F Press; Regina G Ziegler; Robert M Millikan; Sandra L Deming-Halverson; Sarah Nyante; Sue A Ingles; Quinten Waisfisz; Helen Tsimiklis; Enes Makalic; Daniel Schmidt; Minh Bui; Lorna Gibson; Bertram Müller-Myhsok; Rita K Schmutzler; Rebecca Hein; Norbert Dahmen; Lars Beckmann; Kirsimari Aaltonen; Kamila Czene; Astrid Irwanto; Jianjun Liu; Clare Turnbull; Nazneen Rahman; Hanne Meijers-Heijboer; Andre G Uitterlinden; Fernando Rivadeneira; Curtis Olswold; Susan Slager; Robert Pilarski; Foluso Ademuyiwa; Irene Konstantopoulou; Nicholas G Martin; Grant W Montgomery; Dennis J Slamon; Claudia Rauh; Michael P Lux; Sebastian M Jud; Thomas Bruning; Joellen Weaver; Priyanka Sharma; Harsh Pathak; Will Tapper; Sue Gerty; Lorraine Durcan; Dimitrios Trichopoulos; Rosario Tumino; Petra H Peeters; Rudolf Kaaks; Daniele Campa; Federico Canzian; Elisabete Weiderpass; Mattias Johansson; Kay-Tee Khaw; Ruth Travis; Françoise Clavel-Chapelon; Laurence N Kolonel; Constance Chen; Andy Beck; Susan E Hankinson; Christine D Berg; Robert N Hoover; Jolanta Lissowska; Jonine D Figueroa; Daniel I Chasman; Mia M Gaudet; W Ryan Diver; Walter C Willett; David J Hunter; Jacques Simard; Javier Benitez; Alison M Dunning; Mark E Sherman; Georgia Chenevix-Trench; Stephen J Chanock; Per Hall; Paul D P Pharoah; Celine Vachon; Douglas F Easton; Christopher A Haiman; Peter Kraft Journal: Nat Genet Date: 2013-04 Impact factor: 38.330