Dysregulated miR-671-5p/CDR1-AS/CDR1/VSNL1 axis is involved in glioblastoma multiforme

被引:107
作者
Barbagallo, Davide [1 ]
Condorelli, Angelo [1 ]
Ragusa, Marco [1 ]
Salito, Loredana [1 ]
Sammito, Mariangela [1 ]
Banelli, Barbara [2 ]
Caltabiano, Rosario [3 ]
Barbagallo, Giuseppe [3 ]
Zappala, Agata [4 ]
Battaglia, Rosalia [1 ]
Cirnigliaro, Matilde [1 ]
Lanzafame, Salvatore [3 ]
Vasquez, Enrico [3 ]
Parenti, Rosalba [4 ]
Cicirata, Federico [4 ]
Di Pietro, Cinzia [1 ]
Romani, Massimo [2 ]
Purrello, Michele [1 ]
机构
[1] Univ Catania, Unita BioMed Mol Genom & Sistemi Complessi, Dipartimento Sci Biomed & Biotecnol, Sez Biol & Genet G Sichel, Catania, Italy
[2] IRCCS AOU San Martino IST, UOS Epigenet Tumori, Genoa, Italy
[3] Univ Catania, Dipartimento Sci Med Chirurg & Tecnol Avanzate GF, Catania, Italy
[4] Univ Catania, Sez Fisiol, Dipartimento Sci Biomed & Biotecnol, Catania, Italy
关键词
glioblastoma multiforme (GBM); non coding RNAs (ncRNAs); microRNAs (miRNAs); circular RNAs (circRNAs); cell networks; GLOBAL-NETWORK STRUCTURE; MICRORNA TRANSCRIPTOME; MESSENGER-RNA; CIRCULAR RNAS; EXPRESSION; GLIOMA; CELLS; TEMOZOLOMIDE; INTEGRATION; PREDICTION;
D O I
10.18632/oncotarget.6621
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile.
引用
收藏
页码:4746 / 4759
页数:14
相关论文
共 48 条
[1]   CEBPA exerts a specific and biologically important proapoptotic role in pancreatic β cells through its downstream network targets [J].
Barbagallo, Davide ;
Condorelli, Angelo Giuseppe ;
Piro, Salvatore ;
Parrinello, Nunziatina ;
Floyel, Tina ;
Ragusa, Marco ;
Rabuazzo, Agata Maria ;
Storling, Joachim ;
Purrello, Francesco ;
Di Pietro, Cinzia ;
Purrello, Michele .
MOLECULAR BIOLOGY OF THE CELL, 2014, 25 (16) :2333-2341
[2]   Long-term therapy with temozolomide is a feasible option for newly diagnosed glioblastoma: a single-institution experience with as many as 101 temozolomide cycles [J].
Barbagallo, Giuseppe M. V. ;
Paratore, Sabrina ;
Caltabiano, Rosario ;
Palmucci, Stefano ;
Parra, Hector Soto ;
Privitera, Giuseppe ;
Motta, Fabio ;
Lanzafame, Salvatore ;
Scaglione, Giorgio ;
Longo, Antonio ;
Albanese, Vincenzo ;
Certo, Francesco .
NEUROSURGICAL FOCUS, 2014, 37 (06)
[3]   Sox2 Promotes Malignancy in Glioblastoma by Regulating Plasticity and Astrocytic Differentiation [J].
Berezovsky, Artem D. ;
Poisson, Laila M. ;
Cherba, David ;
Webb, Craig P. ;
Transou, Andrea D. ;
Lemke, Nancy W. ;
Hong, Xin ;
Hasselbach, Laura A. ;
Irtenkauf, Susan M. ;
Mikkelsen, Tom ;
deCarvalho, Ana C. .
NEOPLASIA, 2014, 16 (03) :193-206.e25
[4]   Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites [J].
Betel, Doron ;
Koppal, Anjali ;
Agius, Phaedra ;
Sander, Chris ;
Leslie, Christina .
GENOME BIOLOGY, 2010, 11 (08)
[5]   ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks [J].
Bindea, Gabriela ;
Mlecnik, Bernhard ;
Hackl, Hubert ;
Charoentong, Pornpimol ;
Tosolini, Marie ;
Kirilovsky, Amos ;
Fridman, Wolf-Herman ;
Pages, Franck ;
Trajanoski, Zlatko ;
Galon, Jerome .
BIOINFORMATICS, 2009, 25 (08) :1091-1093
[6]   The Somatic Genomic Landscape of Glioblastoma [J].
Brennan, Cameron W. ;
Verhaak, Roel G. W. ;
McKenna, Aaron ;
Campos, Benito ;
Noushmehr, Houtan ;
Salama, Sofie R. ;
Zheng, Siyuan ;
Chakravarty, Debyani ;
Sanborn, J. Zachary ;
Berman, Samuel H. ;
Beroukhim, Rameen ;
Bernard, Brady ;
Wu, Chang-Jiun ;
Genovese, Giannicola ;
Shmulevich, Ilya ;
Barnholtz-Sloan, Jill ;
Zou, Lihua ;
Vegesna, Rahulsimham ;
Shukla, Sachet A. ;
Ciriello, Giovanni ;
Yung, W. K. ;
Zhang, Wei ;
Sougnez, Carrie ;
Mikkelsen, Tom ;
Aldape, Kenneth ;
Bigner, Darell D. ;
Van Meir, Erwin G. ;
Prados, Michael ;
Sloan, Andrew ;
Black, Keith L. ;
Eschbacher, Jennifer ;
Finocchiaro, Gaetano ;
Friedman, William ;
Andrews, David W. ;
Guha, Abhijit ;
Iacocca, Mary ;
O'Neill, Brian P. ;
Foltz, Greg ;
Myers, Jerome ;
Weisenberger, Daniel J. ;
Penny, Robert ;
Kucherlapati, Raju ;
Perou, Charles M. ;
Hayes, D. Neil ;
Gibbs, Richard ;
Marra, Marco ;
Mills, Gordon B. ;
Lander, Eric ;
Spellman, Paul ;
Wilson, Richard .
CELL, 2013, 155 (02) :462-477
[7]  
Caltabiano R, 2013, J NEUROSURG SCI, V57, P139
[8]   VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1α/VEGF and β-catenin/Tcf-4 signaling [J].
Chen, Lingchao ;
Han, Lei ;
Zhang, Kailiang ;
Shi, Zhendong ;
Zhang, Junxia ;
Zhang, Anling ;
Wang, Yongzhi ;
Song, Yijun ;
Li, Yongli ;
Jiang, Tao ;
Pu, Peiyu ;
Jiang, Chuanlu ;
Kang, Chunsheng .
NEURO-ONCOLOGY, 2012, 14 (08) :1026-1036
[9]   CEREBELLAR DEGENERATION-RELATED ANTIGEN - A HIGHLY CONSERVED NEUROECTODERMAL MARKER MAPPED TO CHROMOSOMES-X IN HUMAN AND MOUSE [J].
CHEN, YT ;
RETTIG, WJ ;
YENAMANDRA, AK ;
KOZAK, CA ;
CHAGANTI, RSK ;
POSNER, JB ;
OLD, LJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (08) :3077-3081
[10]   miRGator v3.0: a microRNA portal for deep sequencing, expression profiling and mRNA targeting [J].
Cho, Sooyoung ;
Jang, Insu ;
Jun, Yukyung ;
Yoon, Suhyeon ;
Ko, Minjeong ;
Kwon, Yeajee ;
Choi, Ikjung ;
Chang, Hyeshik ;
Ryu, Daeun ;
Lee, Byungwook ;
Kim, V. Narry ;
Kim, Wankyu ;
Lee, Sanghyuk .
NUCLEIC ACIDS RESEARCH, 2013, 41 (D1) :D252-D257