Hsa_circ_0097009 regulates proliferation, apoptosis, migration and invasion of hepatocellular carcinoma cells via miR-568/RNF38 axis.

BACKGROUND: Circular RNAs (circRNAs), a class of non-coding RNAs, has been proved as an essential driver of hepatocellular carcinoma (HCC) progression. However, the aim of this study is to explore the role of hsa_circ_0097009 (circ_0097009) in HCC progression. METHODS: Ki67 expression in HCC tissues was labeled and examined by IHC assay. Quantitative real-time PCR (qRT-PCR) was applied to assess the expression of circ_0097009, miR-568 and RING finger protein 38 (RNF38). Western blot assay was conducted to analyze protein expression. HCC cell colony formation, proliferation, migration, invasion, angiogenesis ability and apoptosis were determined by colony formation assay, 5-ethynyl-29-deoxyuridine (EdU) assay, wound healing assay, trans well assay, angiogenesis assay and flow cytometry. The interaction between circ_0097009 and miR-568 as well as miR-568 and RNF38 was probed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: We found that circ_0097009 and RNF38 expressions were markedly higher, but miR-568 expression was significantly lower in HCC. Circ_0097009 knockdown blocked HCC cell cloning, proliferation, migration, invasion, angiogenesis and facilitated apoptosis. MiR-568 was a target of circ_0097009 in HCC cells. MiR-568 interference could attenuate the circ_0097009 knockdown-induced inhibition on HCC cells progress. MiR-568 depressed cell clonal formation, proliferation, migration, invasion, angiogenesis and promotion of apoptosis, by targeting RNF38, and RNF38 overexpression reversed the suppression of miR-568 in HCC cells. Also, circ_0097009 knockdown blocked tumor growth in vivoCONCLUSION: Together, this study indicated that the oncogenic function of circ_0097009 in HCC, and circ_0097009/miR-568/RNF38 axis was expected to be a novel therapeutic option for HCC patients (Tab. 1, Fig. 7, Ref. 33). Text in PDF www.elis.sk Keywords: circ_0097009, miR-568, RNF38, hepatocellular carcinoma.

Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway.

OBJECTIVE: To identify the significantly altered circRNAs and mRNAs in thyroid cancer, investigate their target miRNAs and determine their biological functions. METHODS: The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set enrichment analysis (GSEA). The correlative circRNAs and mRNAs were found out through Pearson correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis. The mRNA and protein expressions in thyroid cancer tissues and cells were detected by qRT-PCR and western blot. CircRNA was confirmed by the RNase R digestion and nucleic acid electrophoresis. The target relationships were verified by the dual luciferase reporter assay. Cell viability, invasion and apoptosis were determined by MTT assay, Transwell assay and flow cytometry, respectively. RESULTS: CircNEK6 and FZD8 were significantly up-regulated in thyroid cancer, with strong correlations. The Wnt signaling pathway was activated in thyroid cancer. MiR-370-3p was the common target miRNA of circNEK6 and FZD8, and it was down-regulated in thyroid cancer. Overexpression of circNEK6 and FZD8 could promote the growth and invasion of thyroid cancer cells, while up-regulation of miR-370-3p could suppress thyroid cancer progression and inhibit the Wnt signaling pathway. MiR-370-3p's effect on thyroid cancer cells could be rescued by circNEK6 or FZD8. CONCLUSION: CircNEK6 promoted the progression of thyroid cancer through up-regulating FZD8 and activating Wnt signaling pathway by targeting miR-370-3p.