Abstract
BackgroundBreast cancer is a disease characterized by progressive genetic abnormalities including mutations in tumor suppressor genes and oncogenes, as well as other chromosomal abnormalities. Protein inhibitor of activated signal transducer and activator of transcription 3 (PIAS3) is a member of the PIAS family of transcriptional modulators; its expression is altered in many cancers. Micro-ribonucleic acid (miRNA)-18a acts as an oncogene by negatively regulating PIAS3 and thus modulating the expression of signal transducer and activator of transcription 3 (STAT3) target genes. The aim of this work is to examine the expression levels of PIAS3 gene and miRNA-18a in breast cancer tissues and nearby non-tumor tissues. The samples of breast cancer and paired samples of non-cancerous tissue from the same resected breast were obtained from 25 patients undergoing surgery. Full history taking, complete physical examination, pre-operative fine-needle aspiration cytology or ultrasonic (U/S)-guided core biopsy from the breast mass, final surgical biopsy for pathological examination, and routine laboratory investigations were done. Estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) status were evaluated. Total RNA extraction followed by real-time reverse transcription-polymerase chain reaction (RT-PCR) for quantification of PIAS3 mRNA and miRNA-18a expressions was performed.ResultsThe mean value of PIAS3 mRNA fold expression was significantly lower in the tumor group (5.12 ± 9.85) compared to the normal group (8.38 ± 17.10) (p = 0.040). miRNA-18a fold expression was higher among tumor group (3.5 ± 7.4) than that of normal group (2.5 ± 3), however, it did not reach the level of statistical significance (p = 0.861). miRNA-18a fold expression had negative significant correlation with PIAS3 mRNA fold expression (p = 0.018). A significant association was observed between miRNA-18a expression in breast cancer tissues and the pathological grade of the tumor (p = 0.029).ConclusionsThe results of this study showed that PIAS3 mRNA and miRNA-18a might be of importance in breast cancer development and pathogenesis, and this may be reflected on the treatment strategies targeting STAT3 pathway. However, further studies with larger sample size are needed to validate these observations.
Highlights
Breast cancer is a disease characterized by progressive genetic abnormalities including mutations in tumor suppressor genes and oncogenes, as well as other chromosomal abnormalities
The mean PIAS3 mRNA fold expression was significantly lower in tumor group (5.12 ± 9.85) compared to normal group (8.38 ± 17.10), (p = 0.040), while the mean value of Micro-ribonucleic acid (miRNA)-18a fold expression among tumor group (3.5 ± 7.4) was higher than that of normal group (2.5 ± 3); it did not reach the level of statistical significance (p = 0.861)
A significant association was observed between miRNA-18a expression in breast cancer tissues and the pathological grade of the tumor (p = 0.029)
Summary
Breast cancer is a disease characterized by progressive genetic abnormalities including mutations in tumor suppressor genes and oncogenes, as well as other chromosomal abnormalities. Protein inhibitor of activated signal transducer and activator of transcription 3 (PIAS3) is a member of the PIAS family of transcriptional modulators; its expression is altered in many cancers. Micro-ribonucleic acid (miRNA)-18a acts as an oncogene by negatively regulating PIAS3 and modulating the expression of signal transducer and activator of transcription 3 (STAT3) target genes. The aim of this work is to examine the expression levels of PIAS3 gene and miRNA-18a in breast cancer tissues and nearby non-tumor tissues. Protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3) abbreviated as PIAS3 is a member of the PIAS family of transcriptional modulators. PIAS3 functions as an endogenous inhibitor of activated STAT3 which is a cytoplasmic transcription factor that is activated by tyrosine phosphorylation, leading to dimerization and translocation into the nucleus [2]. It directly binds to many transcription factors and either blocks or enhances their activity [5]
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