A 3'-UTR SNP Mutation Regulates Breast Cancer Metastasis Through Affecting MiR-208a-5p-DAAM1-RhoA Axis

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2019 Mar 27

PMID 30911286

Citations 18

Authors

Jie Mei

Ting Yan

Yifu Huang

Tiansong Xia

Fei Chang

Shuning Shen

Leiyu Hao

Yin Chen

Zhongyuan Wang

Xiaozheng Jiang

Bujie Xu

Yichao Zhu

Affiliations

Soon will be listed here.

Abstract

Background: Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a member of microfilament-related formins and mediates cell motility in breast cancer (BrCa). However, the genetic mutation status of mRNA and its correlation with pathological characteristics are still unclearly. Methods: A patient cohort and BrCa cells were recruited to demonstrate the role of functional SNP in microRNA-208a-5p binding site of 3'-UTR and underlying mechanism in BrCa metastasis.

Methods: A patient cohort and BrCa cells were recruited to demonstrate the role of functional SNP in microRNA-208a-5p binding site of 3'-UTR and underlying mechanism in BrCa metastasis.

Results: The expression and activation of DAAM1 increased markedly in lymphnode metastatic tissues. A genetic variant (rs79036859 A/G) was validated in the miR-208a-5p binding site of 3'-UTR. The G genotype (AG/GG) was a risk genotype for the metastasis of BrCa by reducing binding affinity of miR-208a-5p for the 3'-UTR. Furthermore, the miR-208a-5p expression level was significantly suppressed in lymphnode metastatic tissues compared with that in non-lymphnode metastatic tissues. Overexpression of miR-208a-5p inhibited DAAM1/RhoA signaling pathway, thereby leading to the decrease of the migratory ability.

Conclusion: Overall, the rs79036859 G variant of 3'-UTR was identified as a relevant role in BrCa metastasis via the diversity of miR-208a-5p binding affinity.

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