miR-145–5p as a predictive biomarker for breast cancer stemness by computational clinical investigation.

Background: Breast tumors enriched with breast cancer stem cells (BCSCs), play a crucial role in metastasis and
tumor relapse. Hence, targeting BCSCs may lead to efficacious breast cancer therapy. BCSCs have a unique
expression of stemness markers, including Nanog, POU5F1, SOX2, and CD44, which play a vital role in cancer
stem cell properties. However, the regulation of microRNAs (miRNAs)-mediated cancer stem cell marker expressions
is largely unclear.
Methods: MIENTURNET was used to predict miRNA-target interactions. miR-TV, UALCAN and GEPIA databases
were used to analyze the expression of miR-145–5p and SOX2. Survival analysis was obtained by cBioportal, KM
plotter and Breast Cancer Gene-Expression Miner. RNAComposer was used to perform miRNA-mRNA duplex
prediction. In vitro mRNA and miRNA analysis was performed by qRT-PCR.
Results: It was observed that miR-145–5p was the common miRNA targeting stemness markers. miR-145–5p
expression was found to be lower in breast cancer patients compared to healthy subjects. Based on survival
analysis, low expression of miR-145–5p and high expression of SOX2 led to a poor overall survival rate in breast
cancer patients. Pathway enrichment analysis indicated that SOX2 was highly enriched with transcription factors.
Moreover, SOX2 expression level was also upregulated in axillary metastatic lymph nodules. Further, in vitro
ectopic expression of miR-145–5p by its mimic downregulated the SOX2 expression compared to the control
mimic. Overall, SOX2 was a direct target for miR-145–5p as per the binding and minimal-free energy.
Conclusions: In this study, miR-145–5p targeting SOX2 was identified as a potential predictive biomarker for
breast cancer stemness.