Abstract | BACKGROUND: There are many molecular differences between estrogen receptor α (ERα)-positive and ER-negative breast cancers. Recent analyses have shown that the former can be divided into two subtypes, luminal A and luminal B. These differ in response to endocrine therapy and chemotherapy, and in prognosis. In a previous study, we found that microRNA (miR)-1290 that was significantly down-regulated in luminal A tumors and its potential target arylamine N-acetyltransferase 1 (NAT1). The aim of the present study was to determine whether NAT1 is a bona fide target of miR-1290, and to investigate the impact of NAT1 on breast cancer prognosis. METHODS:
Luciferase reporter assays were employed to validate NAT1 as a putative miR-1290 target gene. Expression of NAT1, ERα, progesterone receptor (PgR) and HER2 was analyzed in 394 breast cancer samples by immunohistochemistry. RESULTS: NAT1 was confirmed to be a direct target of miR-1290. Levels of expression of NAT1 were positively correlated with those of ERα (P < 0.0001) and PgR (P < 0.0001), but negatively correlated with both tumor grade and size (P < 0.0001). Kaplan-Meier analysis showed that the presence of NAT1 was significantly associated with increased overall survival (OS) (P = 0.0416) in these patients. Similarly, significant associations of NAT1 with disease-free survival (DFS) (P = 0.0048) and OS (P = 0.0055) in those patients who received adjuvant endocrine therapy with tamoxifen (n = 176) were found. Moreover, NAT1 was also significantly associated with increased DFS (P = 0.0025) and OS (P = 0.0007) in the subset of lymph node-positive patients (n = 147). Univariate and multivariate analyses showed significant associations between levels of NAT1 and DFS (P = 0.0005 and 0.019, respectively). CONCLUSIONS: We report that miR-1290 directly targets the NAT1 3'-UTR and that NAT1 protein expression is correlated with improved OS of breast cancer patients. NAT1 is a possible prognostic biomarker for lymph node-positive breast cancer. Thus, miR-1290 and its target NAT1 are associated with important characteristics of breast cancer.
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Authors | Yumi Endo, Hiroko Yamashita, Satoru Takahashi, Shinya Sato, Nobuyasu Yoshimoto, Tomoko Asano, Yukari Hato, Yu Dong, Yoshitaka Fujii, Tatsuya Toyama |
Journal | BMC cancer
(BMC Cancer)
Vol. 14
Pg. 990
(Dec 20 2014)
ISSN: 1471-2407 [Electronic] England |
PMID | 25528056
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3' Untranslated Regions
- Biomarkers
- Isoenzymes
- MIRN1290 microRNA, human
- MicroRNAs
- RNA, Messenger
- Arylamine N-Acetyltransferase
- N-acetyltransferase 1
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Topics |
- 3' Untranslated Regions
- Adult
- Aged
- Aged, 80 and over
- Animals
- Arylamine N-Acetyltransferase
(genetics)
- Base Sequence
- Binding Sites
- Biomarkers
- Breast Neoplasms
(drug therapy, genetics, mortality, pathology)
- Female
- Humans
- Isoenzymes
(genetics)
- MicroRNAs
(chemistry, genetics)
- Middle Aged
- Neoplasm Grading
- Neoplasm Metastasis
- Prognosis
- RNA Interference
- RNA, Messenger
(chemistry, genetics)
- Tumor Burden
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