Divergent Activity of the Pseudogene in ER-Positive and Negative Breast Cancer.

Transcripts derived from the function as decoys to adsorb miRNAs targeting the tumor suppressor for degradation, and upregulation is known to inhibit growth in preclinical cancer models. Here, 3'UTR transduction influences PTEN, AKT/mTOR signaling, and tumor progression in estrogen receptor (ER)-positive and -negative breast cancer cells. upregulation decreases gene expression in the ER-positive MCF7 and T47D human breast carcinoma cells and accelerates MCF7 tumor growth Of note, transduction significantly decreases ERα () mRNA and protein levels in MCF7 xenografts with a concomitant increase in hsa-miR-26a, a miRNA known to target In the ER-negative MDA-MB-231 and C3HBA breast cancer cells, upregulation of increases gene expression with no influence on hsa-miR-26a, , or ERα expression. While transduction did not influence the growth rate of human MDA-MB-231 xenografts, upregulation profoundly reduces its metastatic propensity. Furthermore, significantly inhibits the growth rate of ER-negative C3HBA murine breast cancer xenografts. transduction had no influence on doxorubicin cytotoxicity in ER-positive MCF7 cells but an increase in doxorubicin sensitivity was observed in the ER-negative MDA-MB-231 cells. In summary, while upregulation decreased transcript levels and stimulated the growth of ER-positive breast cancers, increased transcript levels and inhibited tumor progression was observed in the ER-negative cells. This report highlights the profound biological activity of in breast cancer, which is dictated by the hormone receptor status. .