Moreover, using an in-house generated gene expression dataset, we experimentally proved that a component of the polycomb-repressive complex 2, the histone methyltransferase enhancer of zeste homolog 2 (EZH2), interacts with miR-214, a well-known prometastatic miR in melanoma and breast cancer, highlighting a miR-214-EZH2 regulatory axis potentially relevant in tumor progression.
We found that miR-214 inhibited breast cancer via targeting RNF8, a newly identified regulator that could promote epithelial-mesenchymal transition (EMT).
This study reveals a possible role of miRNA-214-mediated Taxol resistance, contributing to identify novel therapeutic targets against chemoresistant breast cancers.
Importantly, dysregulation in miR-214 expression is associated with pathological bone conditions such as osteoporosis, osteosarcoma, multiple myeloma, and osteolytic bone metastasis of breast cancer.
Here, we examined the expression profiles of osteoclastogenic miRNAs in human bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM.
Our results demonstrated that miR-214 and miR-218 function as tumor suppressors in breast cancer, and may become biomarkers and potential therapeutic targets in breast cancer.
Moreover, the overexpression of miR‑214 markedly increased cell viability and abrogated the apoptosis triggered by serum starvation, indicating that miR‑214 plays a pivotal role in breast cancer cell growth.
These findings suggest a crosstalk between VDR and miR-214 in regulating hedgehog signaling in breast cancer cells, providing new therapies for breast cancer.
Furthermore, p53, which has been reported to be downregulated in BC, was predicted to be the target gene of miR-214 using bioinformatics software programs.
The expression of miR-214 and uncoupling protein 2 (UCP2) was determined by RT-qPCR and Western blot in breast cancer cells and human breast cancer tissue specimens.
Our data show that circulating, cell-free miR-214 has diagnostic potential in breast cancer as indicator of malignant disease and metastatic spread to regional lymph nodes.
Expression of miR-214 specifically reduced cell proliferation of breast cancer cells and inhibited the invasive potential of a highly metastatic breast cancer cell line.