Abstract
Reportedly, circular RNAs (circRNAs) are crucial regulators in cancer progression. Nonetheless, the molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) has not been fully clarified. Gene expression omnibus (GEO) database was employed to screen out the differentially expressed circRNAs in HCC. qRT-PCR and western blot were executed to detect circ_0001806 expression, miR-193a-5p expression, and MMP16 mRNA and protein expressions in HCC. The effect of circ_0001806 on HCC was analyzed by the CCK-8 method and Transwell experiment. RIP assay, pull-down experiment, and dual-luciferase reporter gene experiment were applied to validate the targeting relationships among circ_0001806, miR-193a-5p, and MMP16. Circ_0001806 was up-modulated in HCC tissues and cell lines. Knockdown of circ_0001806 impeded the multiplication, migration, and invasion of HCC cells. Circ_0001806 could up-regulate MMP16 expression through repressing miR-193a-5p, thereby facilitating the malignant biological behaviors of HCC. Circ_0001806 promoted HCC progression by regulating miR-193a-5p/MMP16 axis.
Highlights
Liver cancer has become the sixth most frequently diagnosed cancer and the fourth leading cause of cancerrelated death in the world [1]
Circ_0001806 targeted miR-193a-5p in hepatocellular carcinoma (HCC) cells To determine the downstream mechanism of circ_0001806 in HCC progression, the starBase database was searched, and it was predicted that miR-193a-5p was a potential downstream target of circ_0001806 (Figure 3A, Supplementary Figure S1)
The findings indicated that matrix metallopeptidase 16 (MMP16) was a direct target of miR-193a-5p, and circ_0001806 could positively regulate MMP16 expression in HCC cells
Summary
Liver cancer has become the sixth most frequently diagnosed cancer and the fourth leading cause of cancerrelated death in the world [1]. Since early HCC is usually asymptomatic, HCC patients are usually at an advanced stage when diagnosed and have missed the opportunity for curative treatment (liver resection or liver transplantation) [2,3]. Prevention, and treatment of HCC, in-depth research into the molecular mechanism of this disease is of great importance. The sequence of circRNAs is conserved, the structure of circRNAs is stable, and the expression of circRNA is tissue-specific [5]. These characteristics endow circRNAs with many potential functions, such as acting as a microRNA (miRNA) sponge, or combining with proteins to form RNA-protein complexes to modulate the function of proteins [6]. The role and mechanism of circRNA in HCC have not been fully clarified
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