PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer

• DOI: 10.3892/ijo.2015.3287
• Publication Date: 2015-12-10T09:34:02Z
• Authors: LI-XU YAN; YAN-HUI LIU; JIAN-WEN XIANG; QI-NIAN WU; LEI-BO XU; XIN-LAN LUO; XIAO-LAN ZHU; CHAO LIU; FANG-PING XU; DONG-LAN LUO; PING MEI; JIE XU; KE-PING ZHANG; JIE CHEN
• Keywords: Triple-negative breast cancer

We have previously shown that dysregulation of miR-21 functioned as an oncomiR in breast cancer. The aim the present study was to elucidate mechanisms by which regulate tumor migration and invasion. applied pathway analysis on genome microarray data target-predicting algorithms for target screening, used luciferase reporting assay confirm direct target. Thereafter, we investigated function gene phosphoinositide-3-kinase, regulatory subunit 1 (α) (PIK3R1), detected PIK3R1 coding protein (p85α) immunohistochemistry RT-qPCR 320 archival paraffin-embedded tissues cancer evaluate correlation their expression with prognosis. First, found suppressed growth, invasiveness, metastatic properties cells. Next, identified a showed it negatively regulated miR-21. Furthermore, demonstrated p85α overexpression phenocopied suppression effects antimiR-21 cell invasion, indicating its suppressor role On contrary, knockdown abrogated antimiR‑21-induced effect Notably, induction increased p85α, accompanied decreased p-AKT level. Besides, antimiR-21/PIK3R1-induced invasiveness cells mediated reversing epithelial-mesenchymal transition (EMT). downregulation 25 (7.8%) patients, associated inferior 5-year disease-free survival (DFS) overall (OS). Taken together, provide novel evidence suppresses invasion partly inhibiting PI3K/AKT activation via targeting EMT defined specific subgroup shorter DFS OS, may require more aggressive treatment.