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.
Highlights
Liver cancer is one of the main causes of cancer-related death, with 905,677 new cases and 830,180 deaths worldwide in 2020 [1]
Gene Expression Omnibus (GEO) database (GSE97332) was adopted to identify differentially expressed circRNAs in Hepatocellular carcinoma (HCC) tissues compared with normal tissues adjacent to HCC
The results showed that when oligo18 primers were used, the relative expression of circ_0000098 was significantly lower than when random primers were used, while the expression of linear SLC30A7 mRNA did not change significantly (Figure 1G)
Summary
Liver cancer is one of the main causes of cancer-related death, with 905,677 new cases and 830,180 deaths worldwide in 2020 [1]. CircRNAs, as reported, are abnormally expressed in various cancers and regulate cancer progression [9, 10]. CircRNAs exerts their biological functions via different mechanisms. It can regulate the expression of the downstream genes by sponging microRNAs (miRNAs) [11, 12]. Circ_0000092 up-regulates HN1 expression through competitively binding with miRNA-338-3p, promoting the progression of HCC [11]. In HCC, whether miR-1204 is modulated by circRNA via competitive endogenous RNA (ceRNA) mechanism is still unclear. 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
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