Introduction: Circular RNAs (circRNAs) are associated with the initiation and progression of cancer. However, the biological functions and underlying mechanism of hsa_circ_0005397 in hepatocellular carcinoma (HCC) have not been fully elucidated.Methods: Hemotoxylin and eosin staining was used to assess histological changes.The expression levels of hsa_circ_0005397, miR-326 and pyruvate dehydrogenase kinase 2 (PDK2) were measured by a quantitative real-time polymerase chain reaction. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. Cell cycle distribution and apoptosis were detected by flow cytometry analysis. Caspase-3 activity was determined by a caspase-3 activity kit. Wound healing and transwell assays were used to evaluate cell migration and invasion. A western blot assay was performed to measure the expression of cyclin D1, p21, matrix metalloproteinase (MMP)2, MMP9, PDK2 and PCNA. The interaction between miR-326 and hsa_circ_0005397 or PDK2 was confirmed by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Xenograft tumor models were established to confirm the role of hsa_circ_0005397 in vivo.Results: Hsa_circ_0005397 and PDK2 were up-regulated, whereas miR-326 was down-regulated in HCC tissues and cells. Hsa_circ_0005397 knockdown inhibited cell proliferation and metastasis, and promoted apoptosis. miR-326 was a direct target of hsa_circ_0005397, and inhibition of miR-326 reversed the inhibitory effect of hsa_circ_0005397 silencing on HCC progression. Moreover, PDK2 was a direct target of miR-326 and PDK2 overexpression abated the anti-cancer roles of miR-326 in HCC. Additionally, hsa_circ_0005397 regulated PDK2 expression by sponging miR-326. Furthermore, hsa_circ_0005397 down-regulation suppressed tumor growth by up-regulating miR-326 and down-regulating PDK2.Conclusions: Hsa_circ_0005397 facilitates HCC progression by regulating the miR-326/PDK2 axis, providing a promising circRNA-targeted therapy for HCC.
CircRNAs participated in regulating hepatocellular carcinoma (HCC), and the regulation function of circRNA adenylosuccinate synthase (circADSS) on HCC development is not clear. RT-qPCR and western blot were performed to detect RNA expression.Cell proliferation was analysed by CCK-8 and EdU assay. Cell cycle distribution was analysed by flow cytometry assay. Cell migration and invasion were measured by transwell assay. Mechanism assays were employed to examine the interaction between miR-431-5p and circADSS, or TOP2A. Xenograft mouse model was constructed for in vivo assay. CircADSS and TOP2A expression were boosted, while miR-431-5p was limited in tumour tissues and cells. CircADSS silencing decreased HCC cell proliferation, cell cycle progression, migration, invasion, as well as EMT.MiR-431-5p inhibitors or ectopic TOP2A expression could restore the effect of cir-cADSS knockdown on HCC progression. There was target relationship between miR-431-5p and circADSS, or TOP2A. Knockdown of circADSS suppressed tumour growth in vivo. CircADSS could regulate HCC cell malignancy by miR-431-5p/TOP2A axis.
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