Circular RNAs (circRNAs) play crucial roles in multiple cancers, including hepatocellular carcinoma (HCC). However, the effects and molecular mechanisms of circ_LRIG3 in HCC remain barely unknown. qRT-PCR assay was employed to detect the levels of circ_LRIG3, LRIG3, miR-449a and ring finger protein 38 (RNF38). RNase R assay and Actinomycin D assay were performed to analyze the characteristics of circ_LRIG3. Colony formation assay and MTT assay were used to evaluate cell proliferation. Flow cytometry analysis and transwell assay were adopted for cell apoptosis and metastasis, respectively. Western blot assay was carried out for the protein levels of Ki67, Snail, E-cadherin, RNF38, Smad2/3 and p-Smad2/3. Murine xenograft model assay was used to explore the role of circ_LRIG3 in vivo. circ_LRIG3 expression was upregulated in HCC tissues and cells. Knockdown of circ_LRIG3 suppressed proliferation, migration and invasion and facilitated cell apoptosis in HCC cells in vitro and blocked tumor growth of HCC in vivo. RNF38 overexpression reversed the effects of circ_LRIG3 knockdown on the malignant behaviors of HCC cells. Moreover, circ_LRIG3 could sponge miR-449a to positively modulate RNF38 expression in HCC cells. circ_LRIG3 knockdown inhibited the progression of HCC cells by sponging miR-449a. In addition, circ_LRIG3 silencing might inhibit the Smad2/3 pathway. circ_LRIG3 facilitated HCC progression by modulation of miR-449a/LRIG3 axis, which might provide a novel method for HCC therapy.
The specific function of microRNA-552 (miR-552) has been investigated in several malignancies, except gastric cancer (GC). Therefore, this study was performed to determine the role of miR-552 in GC.GC tissues and adjacent non-tumor tissues were collected to determine the expressions of miR-552. Quantitative real-time polymerase chain reaction assays (RT-qPCR) and Western blot analysis were carried out to measure expression levels. The regulatory mechanism of miR-552 was explored by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) MTT Assay, and Transwell assays. The binding site between miR-552 and FOXO1 was verified by dual-luciferase reporter assays. Upregulation of miR-552 expression was detected and associated with worse clinical outcomes in GC. Furthermore, high miR-552 expression predicted poor prognosis in GC patients. Functionally, upregulation of miR-552 promoted cell viability, metastasis, epithelial-mesenchymal transition (EMT), and phosphatidylinositol 3-kinase and protein kinase B (PI3K/AKT) pathway in GC. In addition, miR-552 was confirmed to target forkhead box O1 (FOXO1) directly and inversely regulate its expression in GC. Upregulation of FOXO1 reversed the carcinogenesis of miR-552 in GC. In conclusion, miR-552 serves as a tumor promoter in GC through targeting FOXO1 and regulating EMT and PI3K/AKT pathway.
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