Relative expression of miRNA targeting S6K1gene of mTOR signaling cascade in Triple Negative Breast Cancer

Background and Objective: Triple Negative Breast Cancer (TNBC) is a highly aggressive and lethal form of breast cancer. MicroRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally regulate gene expression. Aberrant expression of genes in mTOR pathway and their targeting miRNAs plays an important role in TNBC. The aim of this study was to determine the expression of S6K1 mRNA and its targeting miRNA in TNBC patients. Materials and Methods: miRNAs targeting 3ʹ-UTR of S6K1mRNA was predicted using bioinformatics tools. RNA extraction and cDNA synthesis was performed from 20 TNBC samples and their normal adjacent breast tissues. Finally, quantitative RT-PCR was done and REST® 2009 was used to evaluate the expression of S6K1gene and its targeting miRNA.SPSS v.18 was applied for statistical analysis and p.value <0/05 was considered statistically significantly. Findings: According to bioinformatics prediction, miR-557 was selected targeting S6K1mRNA. The expression analysis indicated miR-557 was significantly down-regulated in TNBC samples by 8 folds while its target, S6K1 wassignificantly up-regulated in 12 samples with an average of 18/3 folds and down-regulated in 8 samples with an average of 4/14 folds up-regulated in 14 samples with an average of 33/4 folds and down-regulated in 6 samples with an average of 2/12 folds (p.value <0/05). Conclusion: We found a correlation between up-regulation of S6K1 gene and down-regulation of miR-557. These results suggest that miR-557 can be used as inhibitory agent for S6K1 in breast cancer targeted therapies. However, more investigations are needed to practically confirm these findings.

Keywords:

Breast cancer , mTOR cascade , S6K1 , miR-557