Long non-coding RNA EPB41L4A-AS2 suppresses progression of ovarian cancer by sequestering microRNA-103a to upregulate transcription factor RUNX1T1

Abstract

New Findings: What is the central question of this study? What is the specific mechanism by which EPB41L4A-AS2 exerts a regulatory role in ovarian cancer? What is the main finding and its importance? Overexpressed EPB41L4A-AS2 inhibited cell proliferation, migration and invasion in ovarian cancer by upregulating RUNX1T1 through downregulation of miR-103a. This study provides new insight into the role of EPB41L4A-AS2 in ovarian cancer. Abstract: Ovarian cancer (OC) is a malignant tumour with a poor prognosis. Emerging evidence has shown that long non-coding RNAs (lncRNAs) are regulators that can be used for prognosis, diagnosis and targeted therapy of cancers. Therefore, our purpose was to investigate the possible regulatory role of the lncRNA EPB41L4A-AS2 in the progression of OC. Initially, EPB41L4A-AS2 expression was determined in OC tissues and matched paracancerous tissues. Then the RNA crosstalk among EPB41L4A-AS2, miR-103a and RUNX1T1 was determined. Subsequently, the expression of EPB41L4A-AS2, miR-103a and RUNX1T1 was up- or downregulated by exogenous transfection in SK-OV-3 cells to investigate their roles in the proliferation, migration, colony formation and invasion of OC cells. Further, the tumour formation ability of nude mice was tested in vivo. EPB41L4A-AS2 was poorly expressed in OC tissues and cells, and microarray data revealed upregulation of miR-103a and downregulation of RUNX1T1 in OC. RUNX1T1 was a target gene of miR-103a and EPB41L4A-AS2 bound to miR-103a. Moreover, EPB41L4A-AS2 increased RUNX1T1 expression by decreasing miR-103a expression. EPB41L4A-AS2-overexpressing SK-OV-3 cells exhibited inhibited proliferation, migration, colony formation and invasion, which was rescued by overexpression of miR-103a or silencing of RUNX1T1. Besides, overexpressed EPB41L4A-AS2 repressed tumour formation in vivo. Altogether, the current study demonstrates that overexpressed EPB41L4A-AS2 can potentially bind to miR-103a to promote the expression of RUNX1T1, thereby inhibiting OC, highlighting the potential of EPB41L4A-AS2 as a target for OC.