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Published in: Molecular Cancer 1/2015

Open Access 01-12-2015 | Research

MiR-320a acts as a prognostic factor and Inhibits metastasis of salivary adenoid cystic carcinoma by targeting ITGB3

Authors: Lijuan Sun, Bodu Liu, Zhaoyu Lin, Yandan Yao, Yanyang Chen, Yang Li, Jianing Chen, Dongsheng Yu, Zhangui Tang, Bosheng Wang, Shuguang Zeng, Song Fan, Youyuan Wang, Yilin Li, Erwei Song, Jinsong Li

Published in: Molecular Cancer | Issue 1/2015

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Abstract

Background

Salivary Adenoid cystic carcinoma (SACC) patients with local invasion and lung metastasis are often resistant to conventional therapy such as operation, chemotherapy and radiotherapy. To explore the underling mechanisms, we studied the roles of miRNA in regulating invasiveness of SACC cells.

Methods

MicroRNA profiling was done in SACC cells with microarray. MiRNA mimics or antisense oligonucleotide was transfected and invasiveness of SACC cells was evaluated by adhesion assay and transwell assay. The target gene of miRNA was identified by luciferase reporter assay and “rescue” experiment. Tumor metastasis was evaluated by BALB/c-nu mice xenografts. MiRNA and its target gene expression were identified by in-situ hybridization and immunohistochemistry respectively, in 302 patients from affiliated hospitals of Sun Yat-sen University and in 148 patients from affiliated hospitals of Central South University, and correlated to the clinicopathological status of the patients.

Results

MiR-320a was down-regulated in high lung metastatic ACCM and SACC-LM cells compared with the corresponding low metastatic ACC2 and SACC-83 cells, and inhibited adhesion, invasion and migration of SACC cells by targeting integrin beta 3 (ITGB3). In vivo, enforced miR-320a expression suppressed metastasis of SACC xenografts. In the two independent sets, miR-320a was downregulated in primary SACCs with metastasis compared to those without metastasis, and low expression of this miRNA predicts poor patient survival and rapid metastasis. Multivariate analysis showed that miR-320a expression was an independent indicator of lung metastasis.

Conclusions

MiR-320a inhibits metastasis in SACCs by targeting ITGB3 and may serve as a therapeutic target and prognostic marker in salivary cancers.
Appendix
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Metadata
Title
MiR-320a acts as a prognostic factor and Inhibits metastasis of salivary adenoid cystic carcinoma by targeting ITGB3
Authors
Lijuan Sun
Bodu Liu
Zhaoyu Lin
Yandan Yao
Yanyang Chen
Yang Li
Jianing Chen
Dongsheng Yu
Zhangui Tang
Bosheng Wang
Shuguang Zeng
Song Fan
Youyuan Wang
Yilin Li
Erwei Song
Jinsong Li
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-015-0344-y

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