Upregulation of microRNA-18b induces phosphatase and tensin homolog to accelerate the migration and invasion abilities of ovarian cancer.

Abstract

Ovarian cancer (OC) is the most common cause of mortality from malignant gynecological cancers. Its lethality is mainly a result of tumors that are difficult to detect at the early stage and a lack of effective systemic therapy for advanced status cancer. MicroRNAs (miRNAs/miRs) are a category of single-stranded non-coding small RNAs that bind to their target mRNAs, and aberrant expression levels of miRNAs may serve key roles in regulating cell migration and invasion of various types of human cancer. Previous studies have demonstrated that miR-18b may function as an oncogene in numerous types of tumors, but its role and molecular mechanism in OC remained unclear. The present study demonstrated for the first time that miR-18b expression was significantly upregulated in OC tissues and cells. An increased miR-18b expression level was positively associated with tumor grade and lymph node metastasis. An in vitro assay revealed that exogenous inhibition of miR-18b expression may markedly inhibit OC cell migratory and invasive activities, whereas overexpression of miR-18b enhanced cell migratory and invasive abilities. Of note, using in silico methodologies and luciferase reporter assays, it was demonstrated that phosphatase and tensin homolog (PTEN) was a direct target of miR-18b in OC cells. Furthermore, knockdown of miR-18b expression may significantly decrease mRNA and protein expression levels of endogenous PTEN. The results of the present study highlighted that upregulation of miR-18b was involved in OC cell metastasis by directly targeting PTEN. Inhibition of miR-18b may be a novel effective diagnostic and therapeutic measure for OC.