MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells

Abstract

Abstract. MicroRNAs (miRs) are a type of small non-coding RNA that serve crucial roles in the development and progression of breast cancer. However, the exact role and underlying molecular mechanism of miR-375 in mediating the growth and metastasis of breast cancer remains unknown. In the present study, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to examine RNA and protein expression. A luciferase reporter assay was performed to determine the association between miR-375 and paired box 6 (PAX6). The results of the current study indicate that the expression of miR-375 was reduced in breast cancer tissues compared with matched adjacent normal tissues. Transfection with miR-375 mimics led to a significant increase in levels of miR-375 in human breast cancer Michigan Cancer Foundation (MCF)-7 cells (P<0.05). The increase in miR-375 expression caused a significant decrease in the viability, migration and invasion of MCF-7 cells (P<0.05), accompanied by a reduced expression of matrix metalloproteinase (MMP) 2 and MMP9 proteins. Luciferase reporter assay identified PAX6 as a novel target of miR-375 and miR-375 in turn, negatively regulated the protein expression of PAX6 in MCF-7 cells. By contrast, overexpression of PAX6 led to a significant increase in MCF-7 cell viability (P<0.01) but did not affect the migration and invasion of MCF-7 cells, suggesting that the inhibitory effect of miR-375 on MCF-7 cell viability may be occurring, in part, via the direct targeting of PAX6.

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

“…Interestingly, other studies have shown that increased expression of miR-34a and miR-375 reduces cell viability of cancer cell lines. 57,58 In this regard, our present data also showed that BAY 11-7082 decreases the levels of "oncomirs", miR-155, miR-192 and miR-21 levels, while increasing the levels of "tumour suppressors", miR-34a and miR-375, raising the view that specific cancer-related miRNAs interactions may be at least partially responsible for decreased cells viability. and -451a in treated hypopharyngeal mucosa.…”

“…The preferential effect of BAY 11‐7082 in acidic bile‐treated groups is especially interesting because it suggests its effect on cell viability is not global but related to specific events, in those groups. Interestingly, other studies have shown that increased expression of miR‐34a and miR‐375 reduces cell viability of cancer cell lines 57, 58. In this regard, our present data also showed that BAY 11‐7082 decreases the levels of “oncomirs”, miR‐155, miR‐192 and miR‐21 levels, while increasing the levels of “tumour suppressors”, miR‐34a and miR‐375, raising the view that specific cancer‐related miRNAs interactions may be at least partially responsible for decreased cells viability.…”

MicroRNA‑758 acts as a tumor inhibitor in colorectal cancer through targeting PAX6 and regulating PI3K/AKT pathway

“…More importantly, upregulation of PAX6 attenuated the inhibitory effect of miR-758 in CRC. In consistency with the results of the present study, PAX6 has also been reported to be upregulated in retinoblastoma and breast cancer (25,26). In particular, as a target of miR-7, PAX6 was found to promote proliferation and invasion of CRC cells (27).…”

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

“…miRNA-320b is down-regulated in various cancers, and it is associated with tumorigenesis and poor prognosis in glioma. 42 miRNA-375 was also shown to be often down-regulated in NSCLC, 43,44 breast cancer, 45 colorectal cancer, [46][47][48][49] oesophageal cancer, 50,51 gastric cancer, 52,53 and pancreatic cancer. 54,55 It is associated with tumour proliferation and metastases.…”