Data from MicroRNA-194 Promotes Prostate Cancer Metastasis by Inhibiting SOCS2

• DOI: 10.1158/0008-5472.c.6509570
• Publication Date: 2023-03-31T02:37:05Z
• Authors: Rajdeep Das; Philip A. Gregory; Rayzel C. Fernandes; Iza Denis; Qingqing Wang; Scott L. Townley; Shuang G. Zhao; Adrienne R. Hanson; Marie A. Pickering; Heather K. Armstrong; Noor A. Lokman; Esmaeil Ebrahimie; Elai Davicioni; Robert B. Jenkins; R. Jeffrey Karnes; Ashley E. Ross; Robert B. Den; Eric A. Klein; Kim N. Chi; Hayley S. Ramshaw; Elizabeth D. Will...; Amina Zoubeidi; Gregory J. Goodall; Felix Y. Feng; Lisa M. Butler; Wayne D. Tilley; Luke A. Selth
• Keywords: SOCS2

<div>Abstract<p>Serum levels of miR-194 have been reported to predict prostate cancer recurrence after surgery, but its functional contributions this disease not studied. Herein, it is demonstrated that a driver metastasis. Prostate tissue were associated with aggressiveness and poor outcome. Ectopic delivery stimulated migration, invasion, epithelial–mesenchymal transition in human cell lines, stable overexpression enhanced metastasis intravenous intraprostatic tumor xenografts. Conversely, inhibition activity suppressed the invasive capacity lines <i>in vitro</i> vivo</i>. Mechanistic investigations identified ubiquitin ligase suppressor cytokine signaling 2 (SOCS2) as direct, biologically relevant target cancer. Low <i>SOCS2</i> correlated strongly clinical specimens. SOCS2 downregulation recapitulated miR-194–driven metastatic phenotypes, whereas nontargetable reduced miR-194–stimulated invasion. Targeting by resulted derepression oncogenic kinases FLT3 JAK2, leading ERK STAT3 signaling. Pharmacologic JAK/STAT pathways reversed phenotypes. The GATA2 transcription factor was an upstream regulator miR-194, consistent strong concordance between Overall, these results offer new insights into molecular mechanisms progression <i>Cancer Res; 77(4); 1021–34. ©2016 AACR</i>.</p></div>