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

Abstract

Abstract. 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.

Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis

“…MiR-21-5p was confirmed to be highly expressed and plays its oncogene roles in a variety of tumors, including BC 16 – 18 . For example, miR-21-5p advanced migration and invasion of cervical carcinoma cells through targeting von Hippel-Lindau tumor suppressor (VHL) gene 19 . But the effects of miR-21-5p on malignant cellular phenotypes of BC are not very clear.…”

Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis

“…In the UM samples, 423 mature miRNAs were shown to be present, of which 13 miRNAs were differentially expressed between low-, intermediate- or, high-risk UM. MiRNAs that are highly expressed in high-risk UM include several known oncomirs such as miRNA-17-5p [25,26,27], miRNA-151a-3p [28], and miRNA-21-5p [29,30,31,32]. MiRNA-17-5p has been described to promote cell proliferation, invasion, and metastasis through several mechanisms, such as PTEN repression, downregulation of EGFR2, and TGFBR2 targeting.…”

Dysregulated microRNA expression profiles in gastric cancer cells with high peritoneal metastatic potential

“…Previous studies have demonstrated that miR-21 may act as an oncogene that is overexpressed and hyperactivated in a variety of cancer types, and that its upregulation promotes the proliferation, apoptosis, invasion and chemoresistance by targeting numerous tumor suppressor genes, including phosphatase and tensin homologue, programmed cell death 4, tissue inhibitor of metalloproteinases 3, tropomyosin 1, ras homolog gene family member B and maspin ( 24 – 28 ). It appears that the majority of studies has considered miR-21-5p a cancer-promoting ‘oncomiRs’ that drives tumor progression and development ( 29 , 30 ). The present study, however, indicated that downregulated miR-21-5p expression may be associated with the peritoneal metastatic potential of gastric cancer cells.…”