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.

Long non-coding RNA PVT1 facilitates cell proliferation by epigenetically regulating FOXF1 in breast cancer

“…9 Moreover, a previous study showed that PVT1-derived miR-1207-5p contributed to breast cancer cells proliferation by negatively regulating STAT6 expression. 25 About 20% of human lncRNAs have been revealed to be physically associated with PRC2 complex, hinting the important roles of lncRNAs in recruiting polycomb-group proteins to their target genes. 26 Previous studies also showed that PVT1 could bind to EZH2, which modulated gene expression by promoting H3K27me3.…”

Long noncoding RNA HAGLR acts as a microRNA‐143‐5p sponge to regulate epithelial‐mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3

“…1F). Among them, miR-143-5p was reported to play an inhibitory role in gallbladder cancer (29), whereas miR-1207 promotes the progression of breast cancer (30). Besides, it has been indicated that miR-661 promotes the development of non-small cell lung cancer (31).…”

Prognostic Significance of LncRNA PVT1 and Its Potential Target Gene Network in Human Cancers: a Comprehensive Inquiry Based Upon 21 Cancer Types and 9972 Cases

“…In recent years, studies on the mechanism of action of PVT1 in cancer have proliferated, and increasing evidence suggested that PVT1 could affect diverse biological behaviors of multiple tumors. Yan et al observed that the expression of PVT1 was positively associated to miR-1207-5p, which promoted the breast cancer cell proliferation by targeting STAT6 [43]. Ma et al revealed that PVT1 was highly expressed in glioma vascular endothelial cells, which increased the expression of Beclin1 and Atg7 by targeting miR-186, thereby promoting cell proliferation, migration and angiogenesis [44].…”