Our results demonstrate that miR-140 acts as a tumor suppressor in breast cancer by inhibiting FEN1 to repress DNA damage repair and reveal miR-140 to be a new anti-tumorigenesis factor for adjunctive breast cancer therapy.
Furthermore, down-regulation of TRPM2-AS and PYCR1 inhibited proliferation yet promoted apoptosis of BC cell, and up-regulation of miR-140-3p in BC cell showed the same tendency.
Among them, miR-140-5p was found to be downregulated in breast cancer and directly targeted GLUT1, resulting in an antiglycolytic and antiproliferative effect.
Significantly higher levels of miR-140-5p, miR-194 and miR-423-5p (the last of which harbours the single-nucleotide polymorphism rs6505162) were seen in the breast tumours of Nigerian patients when compared with other ethnic groups (all p < 0.0001). miR-101 was overexpressed in breast cancers in the Indian patients.
The mRNA amount of miR-140-5p was decreased in the breast cancer clinical samples and breast cancer with metastasis compared with the corresponding adjacent normal tissues and cancer without metastasis.
This miRNA has previously been shown to control stemness of breast cancer cells. miRNAseq data of breast cancer patients (TCGA dataset) showed that both the canonical hsa-miR-140-3p and its 5'isomiR-140-3p were highly expressed in patients' tumors compared to normal breast tissue.
We have used this system to track miR-140 promoter activity in breast cancer cells and to follow the impact of estrogen signaling in cancer stem cell subpopulations.