Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer

Oncogene
Yajuan LiJin Q Cheng

Abstract

Adenomatous polyposis coli (APC) mutation is the most common genetic change in sporadic colorectal cancer (CRC). Although deregulations of miRNAs have been frequently reported in this malignancy, APC-regulated miRNAs have not been extensively documented. Here, by using an APC-inducible cell line and array analysis, we identified a total of 26 deregulated miRNAs. Among them, members of miR-17-92 cluster were dramatically inhibited by APC and induced by enforced expression of β-catenin. Furthermore, we demonstrate that activated β-catenin resulted from APC loss binds to and activates the miR-17-92 promoter. Notably, enforced expression of miR-19a overrides APC tumor suppressor activity, and knockdown of miR-19a in cancer cells with compromised APC function reduced their aggressive features in vitro. Finally, we observed that expression of miR-19a significantly correlates with β-catenin levels in colorectal cancer specimens, and it is associated to the aggressive stage of tumor progression. Thus, our study reveals that miR-17-92 cluster is directly regulated by APC/β-catenin pathway and could be a potential therapeutic target in colon cancers with aberrant APC/β-catenin signaling.

References

Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·P J MorinK W Kinzler
Jan 9, 2001·Virchows Archiv : an International Journal of Pathology·K MiyazawaK Mukai
Jan 30, 2004·Cancer Cell·Maina LepourceletRamesh A Shivdasani
Aug 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yasusei KudoTakashi Takata
Sep 17, 2004·Nature·Victor Ambros
Jun 10, 2005·Nature·Kathryn A O'DonnellJoshua T Mendell
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
Feb 14, 2007·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yuko Mimori-KiyosueShoichiro Tsukita
Aug 25, 2007·Molecular Cancer·Giovanni LanzaMassimo Negrini
Dec 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Xu-Bao ShiRalph W deVere White
Apr 5, 2008·Seminars in Cell & Developmental Biology·Angela I M BarthW James Nelson
Jan 8, 2009·Science Signaling·Jason E Fish, Deepak Srivastava
Dec 17, 2009·Genes & Development·Virginie OliveLin He
Dec 19, 2009·The New England Journal of Medicine·Sanford D Markowitz, Monica M Bertagnolli
Jan 6, 2010·Genes & Development·Gijs van Haaften, Reuven Agami
Mar 23, 2010·Lancet·David CunninghamNaureen Starling
May 4, 2010·Biogerontology·Johannes GrillariRegina Grillari-Voglauer
Jun 10, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fumi Takahashi-Yanaga, Michael Kahn
Jul 24, 2010·Neoplasia : an International Journal for Oncology Research·Berit Bølge Tysnes
Oct 21, 2010·Cancer Prevention Research·Yoshikatsu KogaYasuhiro Matsumura
May 10, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Xiaoya LuoHermann Brenner
Oct 20, 2011·Cancer Research·Siyuan SongLiliana Attisano
Nov 9, 2011·Journal of Surgical Oncology·Ge YuYuan-Lian Wan
Oct 31, 2012·The Journal of Cell Biology·Morten Lindow, Sakari Kauppinen
Apr 1, 2014·The American Journal of Pathology·Hong JiangHuang-Ge Zhang
Sep 17, 2014·World Journal of Biological Chemistry·Jiao-Jiao ZhouLei Zheng

❮ Previous
Next ❯

Citations

Aug 26, 2009·Molecular Cancer·Ponniah SelvakumarRajendra K Sharma
Mar 8, 2017·Journal of Cellular Physiology·Farzad RahmaniSeyed Mahdi Hassanian
Jan 10, 2019·Journal of Cellular Physiology·Zhi-Dong LvFu-Nian Li
Apr 17, 2019·Genes·Ce YuanSubbaya Subramanian
Jul 5, 2017·Genes, Chromosomes & Cancer·Martha L SlatteryRoger K Wolff
Dec 1, 2017·Journal of Cancer Research and Clinical Oncology·Martha L SlatteryJennifer S Herrick
Dec 6, 2019·World Journal of Gastroenterology : WJG·Seol-Hee HanSoo-Cheon Chae
Nov 25, 2018·International Journal of Molecular Sciences·Ovidiu BalacescuAlexandru Irimie
May 8, 2018·Genes and Immunity·Bijun WenElena M Comelli
Jun 3, 2017·BioMed Research International·María Antonia LizarbeJavier Turnay
Sep 11, 2020·Computational and Mathematical Methods in Medicine·Baoliang ZhuJing Yan
Aug 4, 2018·Molecular Cancer Research : MCR·Anna ProssomaritiLuigi Ricciardiello
Feb 13, 2021·International Journal of Molecular Sciences·Victoria A StarkBruce M Boman
Nov 20, 2016·International Journal of Pharmaceutics·Larissa KotelevetsPatrick Couvreur
Jun 13, 2021·Cell Death and Differentiation·Prashanthi RameshJan Paul Medema
Aug 13, 2021·Journal of Biochemical and Molecular Toxicology·Meisam Jafarzadeh, Bahram M Soltani
Sep 23, 2021·Biotechnology and Applied Biochemistry·Sahand MoazzendizajiHamed Mohammadi

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
immunoprecipitation
Transfection
ChIP
electrophoresis

Software Mentioned

Bioconductor
ABI SDS
R

Related Concepts

Related Feeds

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.