Emerging Roles Of hsa-circ-0046600 Targeting The miR-640/HIF-1α Signalling Pathway In The Progression Of HCC

Onco Targets Ther. 2019 Nov 6:12:9291-9302. doi: 10.2147/OTT.S229514. eCollection 2019.

Abstract

Purpose: Circular RNAs (circRNAs) play important roles in the development and progression of various human cancers. hsa-circ-0046600 is a circRNA of unknown function. The purpose of this study was to investigate the biological function of hsa-circ-0046600 in hepatocellular carcinoma (HCC) and elucidate the possible molecular mechanisms of this circRNA.

Materials and methods: GSE97332, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect the expression of hsa-circ-0046600 in HCC tissues and cells. A dual-luciferase reporter assay was used to confirm the interaction between hsa-circ-0046600 and miR-640, and a meta-analysis confirmed the expression of miR-640 in HCC. Bioinformatics was used for the functional analysis of miR-640 target genes. N-cadherin and HIF-1α expression was measured by Western blot analysis.

Results: The expression level of hsa-circ-0046600 in HCC tissue was significantly higher than that in adjacent normal tissue (P < 0.05) and was associated with tumour size, TNM stage and pathological vascular invasion. Moreover, the downregulated expression of hsa-circ-0046600 significantly inhibited the migration of HepG2 and SK-HEP-1 cells. hsa-circ-0046600 is present mainly in the cytoplasm and promotes the expression of proteins such as HIF-1α by competitively binding to miR-640 in HCC, thereby affecting the malignant biological behaviour of liver cancer cells.

Conclusion: hsa-circ-0046600 can be used as a new biomarker for HCC diagnosis and disease progression and provides a potential target for targeted therapy.

Keywords: HCC; HIF-1α; hsa-circ-0046600; miR-640; migration.