Circular RNA Circ_0000098 Elevates ALX4 Expression via Adsorbing miR-1204 to Inhibit the Progression of Hepatocellular Carcinoma

Abstract

BackgroundCircular RNAs (CircRNAs) feature prominently in the progression of various cancers. However, the biological functions of many circRNAs in hepatocellular carcinoma (HCC) are far from fully clarified. This work is performed to decipher the function of circ_0000098 (circSLC30A7) in modulating the progression of HCC and its molecular mechanism.MethodsMicroarray data (GSE97332) were available from the Gene Expression Omnibus (GEO) database, and circRNA differentially expressed in HCC tissues was screened out by GEO2R tool. Circ_0000098, microRNA-1204 (miR-1204), and aristaless-like homeobox-4 (ALX4) mRNA expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), scratch wound healing, and Transwell assays were adopted to determine proliferation, migration, and invasion of HCC cells. ALX4 protein, E-cadherin, N-cadherin, and Vimentin expressions were evaluated by Western blot. In addition, the targeting relationship between miR-1204 and circ_0000098 or ALX4 was studied with dual-luciferase reporter assay and RIP assay.ResultsCirc_0000098 expression level was markedly declined in HCC tissues and cells, and its underexpression was associated with larger tumor size of HCC patients. Knocking down circ_0000098 observably promoted the multiplication, migration, invasion, and epithelial-mesenchymal transition (EMT) of Huh7 and SMMC-7721 cells. Additionally, circ_0000098 was mainly distributed in the cytoplasm of HCC cells, and up-regulated ALX4 expression through competitively decoying miR-1204.ConclusionCirc_0000098, as a competitive endogenous RNA (ceRNA) of miR-1204, upregulates ALX4 expression and suppresses the growth, migration, invasion, and EMT of HCC cells.

Research Progress of circRNAs during Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

“…Additionally, the study found that the knockdown of ALX4 counteracted the inhibitory effect of downregulated miR-1204 on HCC cell proliferation, migration, invasion, and EMT. Therefore, it can be concluded that the has_ circ_0000098/miR-1204/ALX4 regulatory network is involved in the progression of EMT in HCC, and low expression levels of has_circ_0000098 are associated with larger tumor volume and later stage [41] . With further research, has_circ_0000098 holds promise as a reference marker for prognostic prediction in HCC patients.…”

The pivotal role of EMT-related noncoding RNAs regulatory axes in hepatocellular carcinoma

“…In the Table 4 there are highlighted critical pathways that involve circRNAs. In HCC, the levels of circFGGY (circ_0006633) ( Feng et al, 2022 ), circ_0000098 ( Li et al, 2021 ), and circEPB41L2 ( Chen et al, 2021 ) are downregulated in tumor tissues and inhibit EMT, proliferation, migration, and invasion. In summary, authors highlight circFGGY/miR-545-3p/Smad7 ( Feng et al, 2022 ), circ_0000098/miR-1204/ALX4 ( Li et al, 2021 ) and circEPB41L2/miR-590-5p ( Chen et al, 2021 ) axes as being important in HCC.…”