miRNA-130a targets ATG2B and DICER1 to inhibit autophagy and trigger killing of chronic lymphocytic leukemia cells

Cancer Research
Valentina KovalevaMartina Seiffert

Abstract

Toxicity and relapses from the immunochemotherapy used to treat chronic lymphocytic leukemia (CLL) prompt continued interest in gentle but effective targeted treatment options for the mainly elderly population suffering from this disease. Here, we report the definition of critical CLL cell survival pathways that can be targeted by ectopic reexpression of the miRNA genes miR-130a and miR-143 which are widely downregulated in CLL. Notably, miR-130a inhibited autophagy by reducing autophagosome formation, an effect mediated by downregulation of the genes ATG2B and DICER1, the latter of which is a major component of the miRNA silencing machinery. In support of the concept of a fundamental connection between miRNA disregulation and altered autophagic flux in this cancer, we showed that RNA interference-mediated knockdown of DICER1 expression was sufficient to reduce autophagy in primary or established cultures of CLL cells. Together, our findings show that miR-130a modulates cell survival programs by regulating autophagic flux, and they define roles for miR-130a and Dicer1 in a regulatory feedback loop that mediates CLL cell survival.

References

Aug 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·F Caligaris-Cappio, T J Hamblin
Jan 3, 2001·The New England Journal of Medicine·H DöhnerP Lichter
Jul 19, 2006·Birth Defects Research. Part C, Embryo Today : Reviews·Gianpiero Di LevaCarlo M Croce
Oct 31, 2006·The American Journal of Pathology·Simion ChioseaRajiv Dhir
Dec 21, 2006·Cancer Research·Yuri PekarskyCarlo M Croce
Jul 6, 2007·Autophagy·Noboru Mizushima, Tamotsu Yoshimori
Sep 26, 2007·Cancer Science·Yukihiro AkaoTomoki Naoe
Nov 2, 2007·Nature Reviews. Cancer·Robin MathewEileen White
Mar 11, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Richard J FlavinJohn J O'Leary
Jul 30, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federico Caligaris-Cappio, Paolo Ghia
Aug 14, 2008·Carcinogenesis·Shogo TokumaruTakashi Takahashi
Oct 1, 2008·Gynecologic Oncology·Antonio SorrentinoCristiano Ferlini
Dec 4, 2009·Nature Reviews. Cancer·Thorsten ZenzStephan Stilgenbauer
Apr 29, 2010·Cancer Research·Ivan DikicVladimir Kirkin
May 5, 2010·Genome Research·Stefano VoliniaCarlo M Croce
Jun 22, 2010·Nature·Christian BehrendsJ Wade Harper
Jun 25, 2010·Leukemia Research·Lilian AmreinRaquel Aloyz
Jul 1, 2010·Cancer Research·Maria Pia ArrateChristine M Eischen
Jul 7, 2010·Cell·Graziano MartelloStefano Piccolo
Oct 23, 2010·Molecular Cell·Guido KroemerBeth Levine
Feb 5, 2011·Autophagy·Anil G JeggaJianhua Zhang
Feb 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ravi K AmaravadiEileen White
Oct 26, 2011·Leukemia & Lymphoma·Martina SeiffertThorsten Zenz
Sep 12, 2012·Autophagy·Daniel J KlionskyBrian Zuckerbraun

❮ Previous
Next ❯

Citations

Apr 9, 2013·Acta Pharmacologica Sinica·Xin LiJin-ku Bao
Dec 12, 2013·Nature Reviews. Molecular Cell Biology·Jens FüllgrabeBertrand Joseph
Aug 21, 2012·Carcinogenesis·Lisa B Frankel, Anders H Lund
Oct 20, 2012·Endocrine-related Cancer·Justin S GundaraStan B Sidhu
Jun 3, 2014·Journal of Translational Medicine·Jian ZhangHua Tang
May 31, 2014·BioMed Research International·Rossella TitoneCiro Isidoro
Apr 1, 2014·Molecular and Cellular Endocrinology·Vincenza LeoneAlfredo Fusco
Jun 25, 2014·The Journal of Clinical Investigation·Thomas BerteroStephen Y Chan
Sep 27, 2015·Neoplasia : an International Journal for Oncology Research·Yemin WangDavid G Huntsman
Dec 17, 2014·Taiwanese Journal of Obstetrics & Gynecology·Angel ChaoTzu-Hao Wang
Aug 10, 2013·Journal of Cellular Physiology·Silvia PalumboSergio Comincini
Apr 23, 2014·Clinical and Experimental Pharmacology & Physiology·Quanfu XuYi-Gang Li
Apr 17, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Weidong HanWendong Huang
Sep 16, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Suning ChenJian Zhang
Jul 15, 2015·Experimental Cell Research·Xiujuan LiuXiangmei Chen
Jan 17, 2013·Autophagy·Kumsal Ayse TekirdagDevrim Gozuacik
Dec 21, 2012·Cell Cycle·Haiyan ZhaiJingfang Ju
Jan 9, 2016·ScienceOpen Research·Yongfei Yang, Chengyu Liang
Jul 16, 2013·Cell Metabolism·Olivier DumortierEmmanuel Van Obberghen
Feb 18, 2015·Cancer Letters·Xinbing SuiHongming Pan
Jan 9, 2014·Blood·Maria T LarsenJack B Cowland
Oct 14, 2014·Frontiers in Public Health·Katriina HuumonenJukka Juutilainen
Apr 26, 2016·Leukemia Research·María Hernández-SánchezJesús-María Hernández-Rivas
Oct 21, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ruhui HanChunhui Ni

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.