Decreased Expression of Bioinformatically Predicted piwil2-targetting microRNAs, miR-1267 and miR-2276 in Breast Cancer.
OBJECTIVE
Human Piwil2, a member of Piwi subfamily of Argonaute proteins, is primarily expressed in testis, where it regulates self-renewal of germ cells. However, its ectopic expression has been reported with several tumors, including breast cancer. The upregulation of piwil2 in various stages of breast cancer suggested its suitability as a novel tumor biomarker. Considering the vital role of microRNAs (miRNAs) in regulating the expression of most human genes, we hypothesized a concomitant downregulation of the bioinformatically-predicted piwil2-targetting microRNAs in breast cancer.


METHODS
We employed different bioinformatic tools to predict piwil2-targeting miRNAs. Then, from the list of predicted miRNAs, we chose two less studied miRNAs (miR-1267 and miR-2276) for experimental validation. Using a real-time RT-PCR approach, we quantified the relative expression of the miRNAs in 31 pairs of formalin-fixed paraffin-embedded tumor/non-tumor tissue samples.


RESULTS
Our data revealed a noticeable but not statistically significant (P = 0.133) downregulation of miR-1267 in tumor samples, compared to non-tumor samples obtained from the same patients. Downregulation of miR-1267 was more significant in higher grades of malignancies (fold change = 2.39, P = 0.033) and also in lymph nodes containing high-grade tumor cells (fold change = 6.66, P = 0.02).  Interestingly, a significant upregulation of miR-1267 was observed in tumors at high stages (stage 3a, 3b), compared to low stages (stage 2a, 2b) (fold change = 8.05, P = 0.048). Similar patterns of expression alteration were also observed for miR-2276.


CONCLUSIONS
Altogether, our findings suggest a probable tumor suppressor role for miR-1267 and miR-2276 in breast tumor initiation and progression, but a probable promoting role for them in invasion and metastasis.
1)Department of Genetics, Science and Research Branch Islamic Azad University, Tehran, Iran. 2)Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
S
S
Torkashvand
Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Z
Z
Damavandi
ParsGenome Company, Tehran, Iran.
B
B
Mirzaei
Genetic Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran.
M
M
Tavallaei
Department of Pathology, Tehran University of Medical sciences, Tehran, Iran.
M
M
Vasei
Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Seyed Javad
SJ
Mowla
D000328:Adult; D000368:Aged; D060565:Argonaute Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D019295:Computational Biology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007492:Iran; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction
D060565:Argonaute Proteins; D014408:Biomarkers, Tumor; D035683:MicroRNAs; C486868:PIWIL2 protein, human