MiR520c blocks EMT progression of human breast cancer cells by repressing STAT3.

Abstract

Breast cancer is one of the most malignant diseases world-wide and it ranks the first among female cancers. Masses of intrinsic and extrinsic factors, especially the inflammatory factors can lead to breast cancer. Aberrant activation and accumulation of key molecules can lead to inflammation associated carcinogenesis. The signal transducers and activators of transcription 3 (STAT3) is one of them. Therefore, to evaluate the novel molecular mechanisms, STAT3 has become our focus for breast cancer targeted therapy. At present, many tumor suppressing microRNAs have been validated, and are the highlights in research on microRNAs. Thus, we predicted microRNAs which could putatively regulate STAT3 through databases and selected six to screen with Dual-luciferase assay. The result hinted that miR520c could bind with STAT3 3'UTR. We mutated the seed sequence of miR520c on STAT3 3'UTR, which illustrated a reverse effect compared with wild-type of STAT3 3'UTR. Subsequently, STAT3, p-STAT3 and miR520c were assessed in three different grades of breast cancer cells, with the degree of malignancy, we found an escalating trend of STAT3 and p-STAT3, on the contrary, a downward trend of miR520c. We observed STAT3 was deactivated by miR520c. Epithelial to mesenchymal transition (EMT) is a fatal transfer of cancer progression. To find out whether the downregulation of STAT3 can repress breast cancer motility and invasion ability, we detected EMT markers. The result implied a suppression effect on EMT. We overexpressed STAT3 to conduct rescue experiments, the result showed a recovery of STAT3 and EMT characteristics. Cell motility and invasion property were regained as well. In the study, we elucidated miR520c could inhibit breast cancer EMT by targeting STAT3. It can enrich the mechanism of breast cancer and may lay the foundation for breast cancer targeted treatment.