Tumor Cell-Derived Exosomal Circ-0072088 Suppresses Migration and Invasion of Hepatic Carcinoma Cells Through Regulating MMP-16

Abstract

Background: Tumor-derived exosomes (EXOs), commonly differentially expressed in circular RNAs, have been shown to be crucial determinants of tumor progression and may regulate the development and metastasis of hepatic carcinoma (HCC).Methods: Possibly differentially expressed circRNAs in patients with HCC were screened out from the Gene Expression Omnibus (GEO). EXOs were isolated from the culture medium of HCC cells and plasma of patients with HCC, followed by characterization by transmission electron microscope, NanHCCight, and western blotting. Additionally, RNA immunoprecipitation and luciferase reporter gene assays were carried out to explore the molecular mechanism of hsa_circRNA_103809 (circ-0072088) in HCC cells.Results: The screening results showed that circ-0072088 was highly expressed in patients with HCC, and its increase indicated unfavorable prognosis of patients according to quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, circ-0072088 was mainly secreted by HCC cells via EXOs in plasma of such patients, and its high level in plasma EXOs was closely associated with tumor node metastasis (TNM) staging and tumor size. Moreover, HCC-secreted EXOs mediated the degradation of miR-375 via circ-0072088 and upregulated MMP-16, thus suppressing the metastasis of HCC.Conclusion: Upregulated in patients with HCC, circ-0072088 may be an index for diagnosis and prognosis of HCC. In addition, HCC-derived EXOs coated with circ-0072088 might be a treatment for HCC, with the ability to inhibit the metastasis of HCC cells.

CircFGGY Inhibits Cell Growth, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma via Regulating the miR-545-3p/Smad7 Axis

“…Previous studies suggested that circRNAs primarily function as miRNA sponges to regulate gene expression ( Huang et al, 2020 ; Lin et al, 2021 ; Ren et al, 2021 ). By bioinformatics prediction, we identified miR-545-3p as the common target of circFGGY and Smad7.…”

The Biological Functions and Clinical Values of Exosomal Circular RNAs in Hepatocellular Carcinoma

“…Besides, Lin et al. ( 40 ) found a notably decreased 5-year survival rate in those with high circ-0072088. The results indicated that high expression of circ-0072088 was closely correlated with an unfavorable prognosis and may be involved in the development of HCC.…”

“…In another study, the expressions of exosomal circ-0072088, circANTXR1, circTMEM45A, hsa_circ_0061395, and hsa_circ_0004001 were significantly upregulated in patients with HCC and positively correlated with TNM stages and tumor size but not with gender or age. In addition, the expression of circTMEM45A was also related to vascular invasion ( 40 , 42 , 45 , 47 , 56 ). Furthermore, high levels of hsa_circ_0004123 and hsa_circ_0075792 expression were positively correlated with tumor size and the TNM stages, but not with age, gender, and LNM ( 56 ).…”

“…Moreover, Lin et al. ( 40 ) showed that circ-0072088 was mainly secreted by HCC cells via exosomes and its expression was significantly higher in HCC tissues and cells than in paracancerous tissue and healthy hepatic cells, and ROC curve analysis showed that circ-0072088 had a high diagnostic value for HCC, with an AUC of 0.899. Some studies discovered that exosome circTMEM45A, circANTXR1, circ-0004277, and circWHSC1 were all upregulated in HCC tissues and cell lines.…”

Activation of circ_0072088/miR‐1261/PIK3CA pathway accelerates lung adenocarcinoma progression

“…[10][11][12] Through bioinformatic analysis and literature reviews, [13][14][15] the consistent upregulation of circ 0072088 expression in LUAD has persuaded us to further examine its role. Paradoxically, some reports have shown that the downregulation of circ 0072088 in hepatic carcinoma cells derived exosome is associated with tumorigenesis, 16 similarly, its decrease has been reported to be associated with metastasis of colorectal cancer, 17 suggesting that, it is necessary to further explore the expression and function of circ 0072088 in the mechanisms underlying LUAD.…”