CircKIF5B Promotes Hepatocellular Carcinoma Progression by Regulating the miR-192 Family/XIAP Axis

Abstract

BackgroundThe long-term prognosis of HCC (hepatocellular carcinoma) with metastasis remains extremely poor. CircRNAs are promising as critical biological markers in identifying disease mechanisms and developing new effective treatments. However, the role of the aberrant expression of circRNAs in HCC progression remains largely unknown.MethodsCircKIF5B location was investigated by RNA fluorescence in situ hybridization (RNA-FISH). For circRNA determination, RNase R treatment and Real-Time Quantitative RT-PCR (qRT-PCR) were performed. Transwell chamber assays examined the chemotactic migration and invasion of liver cancer cells.ResultsThis study identified the circRNA circKIF5B originating from exons 1, 2, and 3 of the KIF5B gene. Importantly, we found that circKIF5B circRNA, rather than KIF5B linear mRNA, was notably upregulated in liver cancer cell lines and tissues. Moreover, we found that silencing circKIF5B markedly reduced the proliferation, invasion, and metastasis of liver cancer cells by sponging the miR-192 family, thus decreasing the expression of X-linked inhibitor of apoptosis (XIAP).ConclusionOur data demonstrate that circKIF5B can regulate XIAP expression by sponging miR-192 and miR-215 competing for the ceRNA mechanism, indicating that circKIF5B may act as an essential upstream regulator and providing mechanistic evidence to support the view that circKIF5B/miR-192s/XIAP is a promising therapeutic target for treating liver cancer.

CircFOXO3 mediates hypoxia‐induced autophagy of endometrial stromal cells in endometriosis

“…The divergent primers detected circRNAs in cDNA with or without RNase R treatment, demonstrating that the circFOXO3 were truly circular and more stable as compared to their linear counterparts, which were amplified by convergent primers and disappeared after RNase R treatment (Figure 1D). It was worth noting that the amount of circFOXO3 also droped after the treatment of RNase R, suggesting that circFOXO3 might be simply more resistant to digestion compared to the linear product, but not fully resistant to degradation, which is consistent with some other studies 41,42 …”

“…It was worth noting that the amount of circFOXO3 also droped after the treatment of RNase R, suggesting that circFOXO3 might be simply more resistant to digestion compared to the linear product, but not fully resistant to degradation, which is consistent with some other studies. 41,42 To investigate whether circFOXO3 play a role in endometriosis, the expression of circFOXO3 was detected in 25 EcEM, 25 corresponding EuEM, and 23 CoEM. As shown in Figure 1E, circFOXO3 expression was found to be significantly lower in EcEM as compared to CoEM and EuEM, suggesting that reduced expression of circFOXO3 may be involved in the pathological process of ovarian endometriosis.…”

Identification and verification of a prognostic autophagy-related gene signature in hepatocellular carcinoma

“…KIF5B expression is upregulated in HCC cell lines and tissues. Silencing KIF5B can significantly reduce the proliferation, invasion, and metastasis of liver cancer cells 19 . Fas-associated protein with death domain (FADD) is a crucial adapter protein for cell apoptosis in the death receptor pathway.…”

circELMOD3 increases and stabilizes TRIM13 by sponging miR-6864-5p and direct binding to inhibit HCC progression

“… 14 For instance, circKIF5B promotes HCC development through the adsorption of miR-192 and miR-215. 15 Similarly, hsa_circ_0003410 acts as a “molecular sponge” for miR-139-3p, thereby facilitating HCC progression. 16 In addition, circRNAs have also been shown to interact with specific mRNAs to affect their stability, which in turn regulates tumorigenesis and progression.…”