SLC6A1-miR133a-CDX2 loop regulates SK-OV-3 ovarian cancer cell proliferation, migration and invasion.

Abstract

The present study assessed the expression of solute carrier 6 member 1 (SLC6A1) in ovarian cancer (OC) tissues and evaluated the effect of silencing SLC6A1 or caudal type homeobox 2 (CDX2) on the proliferation, migration, and invasion of SK-OV-3 OC cells. The levels of caudal type homeobox 2 (CDX2) and SLC6A1 mRNA were also examined in OC SK-OV-3, OVCAR3 and A2780 cell lines. The mRNA levels of CDX2 and SLC6A1 in SK-OV-3 OC cells were assessed following transection with microRNA (miR) 133a mimics; the mRNA and protein levels of SLC6A1 were determined following the silencing of CDX2, and the mRNA expression of CDX2 was gauged following the silencing of SLC6A1. A luciferase reporter assay was performed to assess the effect of miR133a on the CDX2 and SLC6A1 3′-untranslated regions (3′UTRs). The proliferation, migration and invasion rate of SK-OV-3 cells were then examined following the silencing of CDX2 or SLC6A1. The expression of SLC6A1 was increased in OC compared with adjacent tissue. The expression of CDX2 and SLC6A1 in SK-OV-3 and OVCAR3 cells was increased compared with A2780 cells (P<0.05). The level of CDX2 and SLC6A1 mRNA in SK-OV-3 cells decreased when the cells were transected with the miR133a mimics, compared with a negative control (P<0.05). Transfection with the miR133a mimics significantly reduced the luciferase activity of reporter plasmids with the SLC6A1 or CDX2 3′UTRs (P<0.05). The mRNA level of CDX2 was decreased subsequent to the silencing of SLC6A1; the mRNA and protein level of SLC6A1 were decreased when CDX2 was silenced (P<0.05). The proliferation, migration, and invasion of SK-OV-3 cells were significantly reduced following the silencing of CDX2 or SLC6A1 (P<0.05). CDX2 may therefore be inferred to promote the proliferation, migration and invasion in SK-OV-3 OC cells, acting as a competing endogenous RNA.