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Immunohistochemical determination of the miR-1290 target arylamine N-acetyltransferase 1 (NAT1) as a prognostic biomarker in breast cancer.

AbstractBACKGROUND:
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.
AuthorsYumi Endo, Hiroko Yamashita, Satoru Takahashi, Shinya Sato, Nobuyasu Yoshimoto, Tomoko Asano, Yukari Hato, Yu Dong, Yoshitaka Fujii, Tatsuya Toyama
JournalBMC cancer (BMC Cancer) Vol. 14 Pg. 990 (Dec 20 2014) ISSN: 1471-2407 [Electronic] England
PMID25528056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 3' Untranslated Regions
  • Biomarkers
  • Isoenzymes
  • MIRN1290 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1
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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