microRNA-18b is upregulated in breast cancer and modulates genes involved in cell migration

被引:50
作者
Fonseca-Sanchez, Miguel A. [1 ]
Perez-Plasencia, Carlos [2 ,3 ]
Fernandez-Retana, Jorge [2 ]
Arechaga-Ocampo, Elena [4 ]
Marchat, Laurence A. [5 ,6 ]
Rodriguez-Cuevas, Sergio [7 ]
Bautista-Pina, Veronica [7 ]
Arellano-Anaya, Zaira E. [1 ]
Flores-Perez, Ali [1 ]
Diaz-Chavez, Jose [8 ]
Lopez-Camarillo, Cesar [1 ]
机构
[1] Autonomous Univ Mexico City, Oncogen & Canc Prote Lab, Genom Sci Program, Mexico City 03100, DF, Mexico
[2] Natl Inst Cancerol, Oncogen Lab, Mexico City, DF, Mexico
[3] Univ Nacl Autonoma Mexico, Biomed Unit, Super Studies Fac Iztacala, Mexico City, DF, Mexico
[4] Natl Inst Cancerol, Virus & Canc Lab, Mexico City, DF, Mexico
[5] Natl Polytech Inst, Natl Sch Med & Homeopathy, Mol Biomed Program, Mexico City, DF, Mexico
[6] Natl Polytech Inst, Natl Sch Med & Homeopathy, Biotechnol Network, Mexico City, DF, Mexico
[7] Inst Breast Dis FUCAM, Mexico City, DF, Mexico
[8] UNAM Natl Canc Inst, Unit Biomed Res Canc, Inst Biomed Res, Mexico City, DF, Mexico
关键词
breast cancer; tumor marker; microRNA-18b; expression profiling; transcriptome; cell migration; PROSTATE-SPECIFIC ANTIGEN; LUNG-CANCER; OLFACTORY RECEPTORS; MICROARRAY ANALYSIS; PROGNOSTIC MARKER; EXPRESSION; PROTEIN; PERIOSTIN; IDENTIFICATION; PROLIFERATION;
D O I
10.3892/or.2013.2691
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
microRNAs are small non-coding RNAs of similar to 22 nucleotides that function at post-transcriptional level as negative regulators of gene expression. Aberrant expression of microRNAs could promote uncontrolled proliferation, migration and invasion of human cancer cells. In this study, we analyzed the expression of microRNA-18b (miR-18b) in breast cancer cell lines and in a set of clinical specimens. Our results showed that miR-18b was upregulated in four out of five breast cancer cell lines and also in breast tumors. In order to identify potential gene targets, we carried out transcriptional profiling of MDA-MB-231 breast cancer cells that ectopically expressed miR-18b. Our results showed that 263 genes were significantly modulated in miR-18b-deficient cells (fold change >1.5; P=0.05). We found that knock-down of miR-18b induced the upregulation of 55 olfactory receptor (OR) genes and nine genes (NLRP7, KLK3, OLFM3, POSTN, MAGED4B, KIR3DL3, CRX, SEMG1 and CEACAM5) with key roles in cell migration and metastasis. Consistently, we found that ectopic inhibition of miR-18b suppressed the migration of two breast cancer cell models in vitro. In conclusion, we have uncovered genes directly or indirectly modulated by miR-18b which may represent potential therapeutic targets in breast cancer. Our data also pointed out a role of miR-18b in migration of breast cancer cells.
引用
收藏
页码:2399 / 2410
页数:12
相关论文
共 89 条
[1]   Identification of SCN3B as a novel p53-inducible proapoptotic gene [J].
Adachi, K ;
Toyota, M ;
Sasaki, Y ;
Yamashita, T ;
Ishida, S ;
Ohe-Toyota, M ;
Maruyama, R ;
Hinoda, Y ;
Saito, T ;
Imai, K ;
Kudo, R ;
Tokino, T .
ONCOGENE, 2004, 23 (47) :7791-7798
[2]   Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia [J].
Almalte, Zaema ;
Samarani, Suzanne ;
Iannello, Alexandre ;
Debbeche, Olfa ;
Duval, Michel ;
Infante-Rivard, Claire ;
Amre, Devendra K. ;
Sinnett, Daniel ;
Ahmad, Ali .
BLOOD, 2011, 118 (05) :1323-1328
[3]   Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: a prospective analysis [J].
Arrieta, Oscar ;
Saavedra-Perez, David ;
Kuri, Roberto ;
Aviles-Salas, Alejandro ;
Martinez, Luis ;
Mendoza-Posada, Daniel ;
Castillo, Patricia ;
Astorga, Alma ;
Guzman, Enrique ;
De la Garza, Jaime .
BMC CANCER, 2009, 9
[4]  
Bakker ABH, 1998, J IMMUNOL, V160, P5239
[5]   Biologic tumor behavior in pilocytic astrocytomas [J].
Belirgen, Muhittin ;
Berrak, Su Gulsun ;
Ozdag, Hilal ;
Bozkurt, Suheyla Uyar ;
Eksioglu-Demiralp, Emel ;
Ozek, M. Memet .
CHILDS NERVOUS SYSTEM, 2012, 28 (03) :375-389
[6]   The microRNA.org resource: targets and expression [J].
Betel, Doron ;
Wilson, Manda ;
Gabow, Aaron ;
Marks, Debora S. ;
Sander, Chris .
NUCLEIC ACIDS RESEARCH, 2008, 36 :D149-D153
[7]   The diagnostic and prognostic utility of prostate-specific antigen for diseases of the breast [J].
Black, MH ;
Diamandis, EP .
BREAST CANCER RESEARCH AND TREATMENT, 2000, 59 (01) :1-14
[8]   Regulation of M2, M3, and M4 muscarinic receptor expression in K562 chronic myelogenous leukemic cells by carbachol [J].
Cabadak, Hulya ;
Aydin, Banu ;
Kan, Beki .
JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION, 2011, 31 (01) :26-32
[9]   Expression of Semenogelins I and II and Its Prognostic Significance in Human Prostate Cancer [J].
Canacci, Anastasia M. ;
Izumi, Koji ;
Zheng, Yichun ;
Gordetsky, Jennifer ;
Yao, Jorge L. ;
Miyamoto, Hiroshi .
PROSTATE, 2011, 71 (10) :1108-1114
[10]   Prioritization of driver mutations in pancreatic cancer using cancer-specific high-throughput annotation of somatic mutations (CHASM) [J].
Carter, Hannah ;
Samayoa, Josue ;
Hruban, Ralph H. ;
Karchin, Rachel .
CANCER BIOLOGY & THERAPY, 2010, 10 (06) :582-587