RESUMEN
BACKGROUND: circRNA hsa_circ_0018289-mediated growth and metastasis of CC cells were investigated, as well as the mechanistic pathway. METHODS: Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to examine the expression of hsa_circ_0018289, microRNA (miR)-1294, and isoprenylcysteine carboxyl methyltransferase (ICMT). CC cell proliferation, migration, and invasion were evaluated by 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, transwell assays, Western blot analysis of ICMT, and glycolysis-associated proteins. Dual-luciferase reporter or RNA pull-down analysis of the target interaction between miR-1294 and hsa_hsa_circ_0018289 or ICMT. Xenograft model assay was implemented to assess the role of hsa_circ_0018289 in vivo. Immunofluorescence (IHC) was employed to detect the level of Ki-67. RESULTS: Hsa_circ_0018289 was elevated in CC tissues and cells, its deficiency could repress growth, metastasis, and glycolysis of CC cells in vitro, as well as hamper tumor growth in vivo. Hsa_circ_0018289 sponged miR-1294 while miR-1294 bound with ICMT, and the inhibition of miR-1294 or addition of ICMT could partially relieve the effect caused by hsa_circ_0018289 depletion. CONCLUSION: Hsa_circ_0018289 contributes to malignant development by regulating the miR-1294/ICMT axis, affording novel insight into CC therapy.
Asunto(s)
MicroARNs , Proteína Metiltransferasas , ARN Circular , Neoplasias del Cuello Uterino , Carcinogénesis , Proliferación Celular/genética , Femenino , Humanos , MicroARNs/genética , Proteína Metiltransferasas/genética , ARN Circular/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patologíaRESUMEN
Circular RNAs (circRNAs) are a type of non-coding RNAs that have been identified as critical regulators in various diseases, especially in cancers. However, the expression profiles and functions of circRNAs in cervical cancer are still unclear. In present study, human circRNAs microarray were performed to screen the circRNAs expression in cervical cancer tissue. Microarray analysis revealed 45 significantly expressed circRNAs with 4 fold change. Among these up-regulated circRNAs, hsa_circ_0018289 was validated to be significantly up-regulated in 35 pairs of cervical cancer tissue compared with adjacent normal tissue and cell lines. Loss-of-function experiments revealed that, in vitro and in vivo, hsa_circ_0018289 knockdown inhibited the proliferation, migration and invasion of cervical cancer cells. Via bioinformatics prediction program and luciferase reporter assays, hsa_circ_0018289 was observed to directly bind to miR-497. Taken together, the results indicate that hsa_circ_0018289 plays important role in cervical cancer proliferation, migration and invasion, suggesting the miRNA 'sponge' of hsa_circ_0018289 and its oncogenic role on cervical cancer tumorigenesis.