MicroRNA-21-5p induces the metastatic phenotype of human cervical carcinoma cells in vitro by targeting the von Hippel-Lindau tumor suppressor

Numerous studies have indicated that microRNAs (miRs), a group of small non-coding RNAs, are determining regulatory elements involved in the pathogenesis of various types of cancer, including cervical cancer (CC). Although miR-21-5p upregulation has been demonstrated to associate with tumorigenesis by controlling the expression of oncogenic and tumor suppressor genes, only a small number of studies have investigated the expression of miR-21-5p and its functional role in CC. The objective of the present study was to investigate the effect of miR-21-5p on the proliferation, apoptosis, migration and invasion of CC cells, and the potential underlying molecular mechanism of these effects. The measurement of miR-21-5p levels using quantitative polymerase chain reaction revealed that miR-21-5p was markedly increased in CC cell lines compared with normal cells. Upon silencing of miR-21-5p, a marked suppression of the proliferation, migration and invasion of CaSki cells was observed, with induction of cell apoptosis. These effects were reversed with miR-21-5p overexpression. A database search followed by a luciferase reporter assay ascertained that the 3'-untranslated region of the von Hippel-Lindau tumor suppressor (VHL) mRNA sequence was a direct target of miR-21-5p. Furthermore, silencing of VHL neutralized the effects of miR-21-5p inhibition. These observations suggested that miR-21-5p is an oncogene that is able to promote the metastatic phenotype of CC cells through downregulation of VHL expression, which may present a path to novel therapeutic stratagems for the CC therapy.