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. 2013 Feb;5(2):569-573.
doi: 10.3892/ol.2012.1040. Epub 2012 Nov 22.

rs12976445 variant in the pri-miR-125a correlates with a lower level of hsa-miR-125a and ERBB2 overexpression in breast cancer patients

Tomasz P Lehmann  1 , Konstanty Korski, Mathew Ibbs, Piotr Zawierucha, Sylwia Grodecka-Gazdecka, Paweł P Jagodziński
Affiliations

rs12976445 variant in the pri-miR-125a correlates with a lower level of hsa-miR-125a and ERBB2 overexpression in breast cancer patients

Tomasz P Lehmann et al. Oncol Lett. 2013 Feb.

Abstract

Expression of MIR125A is diminished in breast tumors, however the reason for the hsa-mir-125a decrease in the cancer is not known. HER2 is encoded by ERBB2, a target for hsa-miR-125a which interacts with the 3'UTR of ERBB2 mRNA. The present study reveals that a polymorphism (rs12976445) within the pri-miR-125a sequence correlates with the amount of mature hsa-miR-125a in breast tumor samples. miRNA, RNA and DNA were extracted from breast cancer samples obtained from 26 patients. Following immunohistological evaluation of the samples, the ERBB2, PGR and ESR1 mRNA profiles were also analyzed using real-time PCR. Genomic DNA was sequenced using MIR125A flanking primers. PCR products were analyzed using a BaeGI restriction enzyme specific to the rs12976445 variant. The rs12976445 variant (C/T and C/C) correlated with a lower level of hsa-miR-125a in comparison with the T/T variant. The expression of HER2 mRNA was increased in tumors with the rs12976445 variant (C/T and C/C) compared with T/T. We conclude that rs12976445 may be a potential prognostic marker of HER2 expression in breast cancer. Its predictive value on the efficacy of trastuzumab treatment in patients with HER2-positive breast cancer warrants further study.

Keywords: ERBB2; HER2; breast cancer; miR-125a.

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Figures

Figure 1.
Figure 1.
Sequencing and restriction analysis. (A) rs12976445 in blood and tumor samples, example chromatographs showing the T/T, T/C and C/C variants (arrow). (B) Gel electrophoresis of the restriction enzyme BaeGI (amplicon length, 247 bp) which completely digests the C/C variant (G_KGCM^C,) to 42- and 205-bp fragments. The T/T variant is not digested by BaeGI.
Figure 2.
Figure 2.
hsa-miR-125a and HER2 mRNA levels. Real-time quantification PCR for hsa-miR-125a and ERBB2 (encoding HER2) on samples of tumors from patients. Data are the mean ± SEM from 26 patients. *P<0.05 calculated from a two-sided t-test, T/T variant vs. T/C and C/C variants.
See this image and copyright information in PMC

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