MicroRNA-148a inhibits migration and invasion of ovarian cancer cells via targeting sphingosine-1-phosphate receptor 1

Abstract

MicroRNAs, a group of small non-coding RNA molecules that are involved in gene silencing, function as fine-tuning regulators during cancer progression. MicroRNA (miR)-148a has previously been demonstrated to be associated with ovarian cancer. However, whether miR-148a influences the migration and invasion of ovarian cancer cells has remained elusive. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were conducted to examine mRNA and protein expression levels, respectively. Luciferase reporter assay was used to determine target relationship, and a Transwell assay was used to study cell migration and invasion. The results of the present study indicated that miR-148a expression was markedly downregulated in ovarian cancer tissues compared with that of their matched normal adjacent tissues. In addition, miR-148a expression levels were reduced in three ovarian cancer cell lines, SKOV3, OVCAR and A2780, when compared with those of HUM-CELL-0088 normal ovarian epithelial cells. Furthermore, sphingosine-1-phosphate receptor 1 (S1PR1), which is upregulated in ovarian cancer tissues and cell lines, was identified as a novel target of miR-148a in SKOV3 ovarian cancer cells. The protein expression of S1PR1 was negatively regulated by miR-148a in SKOV3 cells. Furthermore, overexpression of miR-148a or inhibition of S1PR1 suppressed SKOV3 cell migration and invasion, while restoration of S1PR1 expression reversed the suppressive effect of miR-148a upregulation on SKOV3 cell migration and invasion. In conclusion, it was hypothesized that miR-148a may potentially be used as a molecular agent for the prevention and treatment of invasion and metastasis in ovarian cancer, while S1PR1 may present a promising target for clinical applications.