PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6.

Abstract

Accumulating evidence indicates that ectopic expression of non‐coding RNAs are responsible for breast cancer progression. Increased non‐coding RNA PVT1, the host gene of microRNA‐1207‐5p (miR‐1207‐5p), has been associated with breast cancer proliferation. However, how PVT1 functions in breast cancer is still not clear. In this study, we show a PVT1‐derived microRNA, miR‐1207‐5p, that promotes the proliferation of breast cancer cells by directly regulating STAT6. We first confirm the positive correlated expression pattern between PVT1 and miR‐1207‐5p by observing consistent induced expression by estrogen, and overexpression in breast cancer cell lines and breast cancer patient specimens. Moreover, silence of PVT1 also decreased miR‐1207‐5p expression. Furthermore, increased miR‐1207‐5p expression promoted, while decreased miR‐1207‐5p expression suppressed, cell proliferation, colony formation, and cell cycle progression in breast cancer cell lines. Mechanistically, a novel target of miR‐1207‐5p,STAT6, was identified by a luciferase reporter assay. Overexpression of miR‐1207‐5p decreased the levels of STAT6, which activated CDKN1A and CDKN1B to regulate the cell cycle. We also confirmed the reverse correlation of miR‐1207‐5p and STAT6 expression levels in breast cancer samples. Therefore, our findings reveal that PVT1‐derived miR‐1207‐5p promotes the proliferation of breast cancer cells by targeting STAT6, which in turn controls CDKN1A and CDKN1B expression. These findings suggest miR‐1207‐5p might be a potential target for breast cancer therapy.