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Association between miR-125a rs12976445 and survival in breast cancer patients.

ABSTRACT: MicroRNAs (miRNAs) act as an oncogene or a tumor suppressor by negatively regulating target genes. Genetic variants in miRNA genes confer susceptibility to cancer and risk of death in cancer patients. The aim of this study was to investigate whether miRNA polymorphisms were associated with survival in breast cancer patients. Five miRNA polymorphisms (miR-26a1 rs7372209, miR-125a rs12976445, miR-218 rs11134527, miR-423 rs6505162, and miR-608 rs4919510) were genotyped in 196 breast cancer patients. We found that miR-125a rs12976445 was significantly associated with survival in codominant, recessive, and dominant models. However, only association under the codominant model remained significant after adjustment for lymph node metastasis, TNM stage, estrogen receptor, and progesterone receptor. Furthermore, this effect remained in stratification analysis. In conclusion, our results provide evidence that miR-125a rs12976445 may serve as a prognostic biomarker for breast cancer. Further large-scale studies are required to confirm these findings.

SUBMITTER: Jiao L

PROVIDER: S-EPMC4297354 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Association between miR-125a rs12976445 and survival in breast cancer patients.

Jiao Lianghe L Zhang Jiaxin J Dong Yuanyuan Y Duan Bensong B Yu Hong H Sheng Haihui H Huang Junxing J Gao Hengjun H

American journal of translational research 20141122 6

MicroRNAs (miRNAs) act as an oncogene or a tumor suppressor by negatively regulating target genes. Genetic variants in miRNA genes confer susceptibility to cancer and risk of death in cancer patients. The aim of this study was to investigate whether miRNA polymorphisms were associated with survival in breast cancer patients. Five miRNA polymorphisms (miR-26a1 rs7372209, miR-125a rs12976445, miR-218 rs11134527, miR-423 rs6505162, and miR-608 rs4919510) were genotyped in 196 breast cancer patients ...[more]

PMID: 25628797

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Project description:We reported that the class I HDAC inhibitor entinostat induced apoptosis in erbB2-overexpressing breast cancer cells via downregulation of erbB2 and erbB3. Here, we study the molecular mechanism by which entinostat dual-targets erbB2/erbB3. Treatment with entinostat had no effect on erbB2/erbB3 mRNA, suggesting a transcription-independent mechanism. Entinostat decreased endogenous but not exogenous erbB2/erbB3, indicating it did not alter their protein stability. We hypothesized that entinostat might inhibit erbB2/erbB3 protein translation via specific miRNAs. Indeed, entinostat significantly upregulated miR-125a, miR-125b, and miR-205, that have been reported to target erbB2 and/or erbB3. Specific inhibitors were then used to determine whether these miRNAs had a causal role in entinostat-induced downregulation of erbB2/erbB3 and apoptosis. Transfection with a single inhibitor dramatically abrogated entinostat induction of miR-125a, miR-125b, or miR-205; however, none of the inhibitors blocked entinostat action on erbB2/erbB3. In contrast, co-transfection with two inhibitors not only reduced their corresponding miRNAs, but also significantly abrogated entinostat-mediated reduction of erbB2/erbB3. Moreover, simultaneous inhibition of two, but not one miRNA significantly attenuated entinostat-induced apoptosis. Interestingly, although the other HDAC inhibitors, such as SAHA and panobinostat, exhibited activity as potent as entinostat to induce growth inhibition and apoptosis in erbB2-overexpressing breast cancer cells, they had no significant effects on the three miRNAs. Instead, both SAHA- and panobinostat-decreased erbB2/erbB3 expression correlated with the reduction of their mRNA levels. Collectively, we demonstrate that entinostat specifically induces expression of miR-125a, miR-125b, and miR-205, which act in concert to downregulate erbB2/erbB3 in breast cancer cells. Our data suggest that epigenetic regulation via miRNA-dependent or -independent mechanisms may represent a novel approach to treat breast cancer patients with erbB2-overexpressing tumors.

Dataset Information

Association between miR-125a rs12976445 and survival in breast cancer patients.

Publications

Association between miR-125a rs12976445 and survival in breast cancer patients.

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