Circ_0091579 Knockdown Inhibited HCC Proliferation and Glutamine Metabolism Through miR-1270/YAP1 Axis

A growing number of studies have indicated that circRNAs play an important role in the progression of malignant tumors, including hepatocellular carcinoma (HCC). In this study, we designed to explore the abnormal expression of hsa_circ_0091579 (circ_0091579) and its role in the pathogenesis of HCC. In this study, the mRNA levels of circ_0091579, miR-1270, and Yes-associated protein (YAP1) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R and Actinomycin D were used to test the stability of circ_0091579. Cell Counting Kit-8 (CCK-8) was used to measure cell viability. Tubule formation assay was used to determine the effect of HCC cells on the number of tubes. Cell apoptosis was detected by flow cytometry. Western blot was used for the protein levels. Transwell and wound healing tests were used to measure the abilities of invasion and migration. The effect of circ_0091579 knockdown on tumor growth was verified in vivo by xenograft tumor assay and Immunohistochemistry (IHC) analysis. Dual-luciferase reporter or RIP assay was used to detect the relationship between miR-1270 and circ_0091579 or YAP1. Glutamine metabolism was determined by ELISA and western blot assays. In the present study, we found that circ_0091579 was upregulated in HCC tissues and cells. Inhibited circ_0091579 expression significantly suppressed proliferation and promoted apoptosis of HCC cells. Moreover, circ_0091579 knockdown inhibited tumor growth in vivo. Bioinformatic prediction and luciferase assay showed that circ_0091579 acted as a molecular sponge for miR-1270 and YAP1 was a target gene of miR-1270. MiR-1270 silencing could reverse the inhibitory effect of circ_0091579 knockdown on HCC progression, and YAP1 overexpression also could reverse the suppressive effect of circ_0091579 silencing on HCC progression. Meanwhile, miR-1270 inhibitor could invert the negative regulation effect of circ_0091579 silencing on YAP1 expression. Circ_0091579 promoted HCC progression by regulating the miR-1270/YAP1 axis, and our study might offer novel biomarkers and therapeutic targets for HCC.

Automated summary

This study found that circ_0091579 is upregulated in HCC and inhibiting its expression can suppress cell proliferation and promote apoptosis in HCC cells, as well as inhibit tumor growth. Circ_0091579 promotes HCC progression by regulating the miR-1270/YAP1 axis.