Star-PAP regulates tumor protein D52 through modulating miR-449a/34a in breast cancer

Abstract

Tumor protein D52 (TPD52) is an oncogene amplified and overexpressed in various cancers. Tumor-suppressive microRNA-449a and microRNA-34a (miR-449a/34a) were recently reported to inhibit breast cancer cell migration and invasion via targeting TPD52. However, the upstream events are not clearly defined. Star-PAP is a non-canonical poly (A) polymerase which could regulate the expression of many miRNAs and mRNAs, but its biological functions are not well elucidated. The present study aimed to explore the regulative roles of Star-PAP in miR-449a/34a and TPD52 expression in breast cancer. We observed a negative correlation between the expression of TPD52 and Star-PAP in breast cancer. Overexpression of Star-PAP inhibited TPD52 expression, while endogenous Star-PAP knockdown led to increased TPD52. Furthermore, RNA immunoprecipitation assay suggested that Star-PAP could not bind to TPD52, independent of the 3’-end processing. RNA pull-down assay showed that Star-PAP could bind to 3’region of miR-449a. In line with these results, blunted cell proliferation or cell apoptosis caused by Star-PAP was rescued by overexpression of TPD52 or downregulation of miR-449a/34a. Our findings identified that Star-PAP regulates TPD52 by modulating miR-449a/34a, which may be an important molecular mechanism underlying the tumorigenesis of breast cancer and provide a rational therapeutic target for breast cancer treatment.