"LPA Regulates SOX9 in Ovarian Cancer Cells

Abstract

1. Abstract Objective: SOX9 is a master transcription factor that regulates development and stem cell programs. This work is to determine SOX9’s potential oncogenic activity and regulatory mechanisms controlling SOX9 protein expression in Epithelial Ovarian Cancer (EOC). Methods: An oncolipid, Lysophoaphatidic Acid (LPA) has been tested for its regulatory effect on SOX9 in mouse and human EOC cells. The CRISPR/Cas9 technique was used to knockout (KO) SOX9. The functional assays of SOX9 in EOC include proliferation, anoikis, CD44 expression, and spheroid-formation. Results: LPA dose- and time-dependently up-regulated SOX9 in EOC cells. This up-regulation was likely mediated by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR γ ) . SOX9 was involved in cellular activities related to Cancer Stem Cells (CSC), including anokis-resistance, regulation CSC marker CD44, and spheroid-formation. Conclusion: Our data revealed that LPA is a regulator of SOX9, thatis involved in stem cell related activates in EOC. Hence, SOX9, along with its regulatory and signaling pathways, warrants further investigation to critically evaluate their therapeutic significance in EOC. Key words ： <span style=font-size:10.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:simsun=>Cancer stem cells (CSC); Epithelial ovarian cancer (EOC), Gynecological cancers, High grade serous ovarian cancer (HGSOC); Lysophosphatidic acid (LPA), Sex determining region Y-box9 (SOX9); Peroxisome proliferator-activated receptor gamma (PPAR