OncoTargets and Therapy (Nov 2019)
Emerging Roles Of hsa-circ-0046600 Targeting The miR-640/HIF-1α Signalling Pathway In The Progression Of HCC
Abstract
Zhensheng Zhai,1 Qiang Fu,1 Chuanjiang Liu,1 Xu Zhang,1 Pengchong Jia,1 Peng Xia,1 Pan Liu,1 Shixiu Liao,2 Tao Qin,1 Hongwei Zhang1 1Department of Hepato-Biliary-Pancreatic Surgery, People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital), Zhengzhou, Henan 450000, People’s Republic of China; 2Department of Institute of Genetics, People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital), Zhengzhou, Henan 450000, People’s Republic of ChinaCorrespondence: Hongwei ZhangDepartment of Hepato-Biliary-Pancreatic Surgery, People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital), Zhengzhou, Henan 450000, People’s Republic of ChinaTel/fax +86-0371-6558-0365Email [email protected]: 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: hsa-circ-0046600, miR-640, HIF-1α, migration, HCC
