Downregulation of SOX9 suppresses breast cancer cell proliferation and migration by regulating apoptosis and cell cycle arrest.

Abstract

SRY-related high-mobility group box 9 (SOX9) is an important transcriptional factor that regulates diverse genes involved in development and stemness. Dysregulation of SOX9 encourages carcinogenesis in various types of cancer, including breast cancer. The present study aimed to explore the role of SOX9 in triple-negative breast cancer (TNBC). SOX9 expression was significantly upregulated in the TNBC MDA-MB-231, MDA-MB-436 and MDA-MB-468 cell lines compared with that in BT-549 cells. Based on a lentivirus assay, SOX9 inhibition in MDA-MB-231 and MDA-MB-436 cells suppressed cell proliferation and colony formation. Apoptosis was increased and the cell cycle was arrested at the G0/G1 phase in SOX9-knockdown cells. Transwell and wound-healing assays demonstrated that SOX9 inhibition decreased the migration and invasion of MDA-MB-231 and MDA-MB-436 cells. RNA sequencing identified that numerous genes were regulated by SOX9, including nucleophosmin, thioredoxin reductase 1, succinate dehydrogenase complex subunit D, nuclear receptor binding SET domain protein 2, eukaryotic translation initiation factor 4γ1 and glycogen phosphorylase L. Overall, the current study suggested that SOX9 acted as an oncogene in TNBC.