Circular RNA hsa_circ_0005397 promotes hepatocellular carcinoma progression by regulating the miR-326/PDK2 axis.

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. 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. 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. Hsa_circ_0005397 facilitates HCC progression by regulating the miR-326/PDK2 axis, providing a promising circRNA-targeted therapy for HCC.

Gong J ，Du C ，Sun N ，Xiao X ，Wu H ... -  《-》

hsa_circ_0091570 acts as a ceRNA to suppress hepatocellular cancer progression by sponging hsa-miR-1307.

Alterations in circular RNA (circRNA) expression have a vital impact on the biological processes in cancer. Moreover, the expression pattern and roles of circRNAs in hepatocellular cancer (HCC) remain unclear. This study performed qRT-PCR to determine the regulated circRNAs in HCC tissues and cell lines. CCK8, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation, cell cycle assay, apoptotic assay, transwell, and wound healing assay were conducted to assess the function of hsa_circ_0091570 or miR-1307 on cell proliferation, apoptosis, and migration in vitro. Mouse xenograft models were used to measure the functions of hsa_circ_0091570 in vivo. The decreased expression of hsa_circ_0091570 was associated with the pathological staging of HCC patients. Furthermore, inhibition of hsa_circ_0091570 promoted cell proliferation and migration, blocked cell apoptosis in HCC cell lines, and promoted tumor growth in the mouse xenograft model. RNA immunoprecipitation assay verified the interaction of hsa_circ_0091570 and miR-1307. The miR-1307 inhibitor inhibited the function induced by hsa_circ_0091570 siRNA. Overall, hsa_circ_0091570 sponge miR-1307 as a ceRNA and regulate ISM1 expression by exerting functional roles in HCC.

Wang YG ，Wang T ，Ding M ，Xiang SH ，Shi M ，Zhai B ... -  《-》

Circular RNA hsa_circ_103809 suppresses hepatocellular carcinoma proliferation and invasion by sponging miR-620.

Li X ，Shen M 《-》

Silencing of hsa_circ_0101145 reverses the epithelial-mesenchymal transition in hepatocellular carcinoma via regulation of the miR-548c-3p/LAMC2 axis.

Jin J ，Liu H ，Jin M ，Li W ，Xu H ，Wei F ... -  《Aging-US》

Circ_0091581 Promotes the Progression of Hepatocellular Carcinoma Through Targeting miR-591/FOSL2 Axis.

Circular RNAs (circRNAs) have shown crucial regulatory roles in cancer biology. We aimed to uncover the role and underlying mechanism of circ_0091581 in hepatocellular carcinoma (HCC) progression. The abundance of circ_0091581, microRNA-591 (miR-591) and FOS like 2, AP-1 transcription factor subunit (FOSL2) was measured by quantitative real-time polymerase chain reaction. Cell viability, colony formation ability, and invasion ability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and transwell invasion assay. The migration ability was analyzed by transwell migration assay and wound healing assay. Flow cytometry was used to evaluate the cell cycle and apoptosis of HCC cells. The interaction between miR-591 and circ_0091581 or FOSL2 was predicted by Circular RNA Interactome database or TargetScan database and confirmed by dual-luciferase reporter assay and RNA immune co-precipitation assay. FOSL2 protein expression was measured by Western blot assay. Xenograft tumor assay was conducted to analyze the role of circ_0091581 in HCC tumor growth in vivo. Circ_0091581 was highly expressed in HCC tissue samples and cell lines in contrast to that in adjacent normal tissue samples and THLE-2 cell line. Circ_0091581 accelerated the viability, colony formation, metastasis, and cell cycle, while it impeded the apoptosis of HCC cells. MiR-591 bound to circ_0091581, and circ_0091581 knockdown-mediated effects in HCC cells were largely overturned by miR-591 silencing. FOSL2 was a target of miR-591, and FOSL2 overexpression largely reversed miR-591 accumulation-induced influences in HCC cells. FOSL2 protein expression was down-regulated by circ_0091581 silencing, and the addition of miR-591 inhibitor partly recovered the expression of FOSL2 in HCC cells. Circ_0091581 interference notably suppressed HCC tumor growth in vivo. Circ_0091581 acted as an oncogene to enhance the viability, colony formation, metastasis and cell cycle and inhibit the apoptosis of HCC cells through targeting miR-591/FOSL2 axis.

Ji C ，Hong X ，Lan B ，Lin Y ，He Y ，Chen J ，Liu X ，Ye W ，Mo Z ，She Z ，Lin S ... -  《-》