In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. LB-467-LB-467
Abstract:
The metastatic spread of tumor cells is ultimately responsible for the vast majority of cancer related mortality. In the attainment of a metastatic phenotype, several intricately interwoven processes are involved that lead to uncontrolled proliferation, loss of intracellular adhesions, extracellular matrix degradation, intravasation and dissemination into distant organs. Therefore, an improved understanding of molecular mechanisms which regulate metastatic transformation and progression of the cancer cells is of paramount importance. In this present study we performed miRNA-microarray analysis of six patient samples comprising normal, primary tumor and distant metastasis tissues, where we found miR-135b, miR-210, miR-378, miR-19a to be significantly up-regulated in both tumor and metastasized tissues as compared to the respective normal equivalents. We validated miR-135b and -210 in a series of 30 colorectal patients, in which we were able to demonstrate an increased expression in tumor as compared to normal tissues (p=0.008 and p=0.03, respectively). Forced in vitro expression of these miRNAs resulted in increased migration and invasion of Rko, SW480 and SW620 colorectal cancer (CRC) cell lines. Additionally, these cells manifested a gain of mesenchymal marker (N-cadherin) and a loss of epithelial marker (E-cadherin) expression at the protein level. Furthermore, of the several predicted targets identified, through luciferase, RT-PCR and Western blot analysis we found SIAH1 and SETD2 to be regulated by miR-135b and -210, respectively. Furthermore, in vivo, chorioallantoic membrane (CAM) metastasis assays revealed that miR-135b and miR-210 significantly induce distant metastasis to the lungs and liver (p=0.05). Our preliminary findings suggest that miR-135b and 210 play important roles in inducing tumor progression and may be useful as potential targets for mitigating metastatic spread Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-467. doi:1538-7445.AM2012-LB-467
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-LB-467
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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