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Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs which are mainly formed by reverse splicing of precursor mRNAs. They are relatively stable and resistant to RNase R because of their covalently closed structure without 5’ caps or 3’ poly-adenylated tails. CircRNAs are widely expressed in eukaryotic cells and show tissue, timing, and disease specificity. Recent studies have found that circRNAs play an important role in many diseases. In particular, they affect the proliferation, invasion and prognosis of cancer by regulating gene expression. CircRNA Forkhead box O3 (circFOXO3) is a circRNA confirmed to be abnormally expressed in a variety of cancers, including prostate cancer, hepatocellular carcinoma, glioblastoma, bladder cancer, and breast cancer, etc. At present, the feature of circFOXO3 as a molecular sponge is widely studied to promote or inhibit the development of cancers. However, the diverse functions of circFOXO3 have not been fully understood. Hence, it is important to review the roles of circFOXO3 in cancers. This review has summarized and discussed the roles and molecular mechanism of circFOXO3 and its target genes in these cancers, which can help to enrich our understanding to the functions of circRNAs and carry out subsequent researches on circFOXO3.

Background. Tryptophan-2,3-dioxygenase (TDO2) converts tryptophan into kynurenine in the initial limiting step of the kynurenine pathway. During the past decade, the overexpression of TDO2 has been found in various human tumors. However, the role of TDO2 in hepatocellular carcinoma is controversial, and we sought to clarify it in this study. Methods. Western blot analysis and immunochemistry were used to detect the expression of TDO2 in human tissue specimens. The effect of TDO2 on cell proliferation in vitro was assessed using CCK8 and colony formation assays, and a xenograft mouse model was used to detect the effect of TDO2 on tumor growth in vivo. Flow cytometry was used to assess the cell cycle status. Results. Low TDO2 expression was found in HCC and was associated with poor prognosis and adverse clinical outcomes. Conversely, TDO2 could restrain the proliferation of HCC cells in vivo and in vitro. Furthermore, TDO2 upregulated the expression of p21 and p27, inducing cell-cycle arrest. Conclusions. The loss of TDO2 expression in HCC was correlated with a poor prognosis and adverse clinical outcomes. At the same time, TDO2 could restrain the growth of HCC in vivo and in vitro. The results indicate that TDO2 is a potential biomarker and therapeutic target for HCC.

RHO GTPases are a subfamily of the RAS superfamily of proteins, which are highly conserved in eukaryotic species and have important biological functions, including actin cytoskeleton reorganization, cell proliferation, cell polarity, and vesicular transport. Recent studies indicate that RHO GTPases participate in the proliferation, migration, invasion and metastasis of cancer, playing an essential role in the tumorigenesis and progression of hepatocellular carcinoma (HCC). This review first introduces the classification, structure, regulators and functions of RHO GTPases, then dissects its role in HCC, especially in migration and metastasis. Finally, we summarize inhibitors targeting RHO GTPases and highlight the issues that should be addressed to improve the potency of these inhibitors.

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Liver cancer is one of the most common solid tumours, and ranks as the third leading cause of cancer‐associated mortality around the world. This study has linked RNF12 to the pathogenesis of liver cancer. Based on the analysis of patient samples and database data, high RNF12 expression was found in liver cancer, in correlation with worse clinicopathological features and a poor prognosis. Meantime, RNF12 could promote the progression of liver cancer in vitro and in vivo. Mechanistically, RNF12 could interact with EGFR and decrease the internalization of EGFR to activate EGF/EGFR signalling. In addition, PI3K‐AKT signalling takes part in the regulation of liver cancer cell proliferation and migration of RNF12. And AKT inhibitor MK2206 could reverse RNF12‐mediated cellular proliferation and migration in liver cancer. The possibility of the physical interaction between RNF12 and EGFR might lay a foundation to develop intervention strategies for liver cancer prevention and therapy.

As a member of the TRIM protein family, TRIM27 is a RING-mediated E3 ubiquitin ligase that can mark other proteins for degradation. Its ubiquitination targets include PTEN, IκBα and p53, which allows it to regulate many signaling pathways to exert its functions under both physiological and pathological conditions, such as cell proliferation, differentiation and apoptosis. During the past decades, TRIM27 was reported to be involved in many diseases, including cancer, lupus nephritis, ischemia-reperfusion injury and Parkinson’s disease. Although the research interest in TRIM27 is increasing, there are few reviews about the diverse roles of this protein. Here, we systematically review the roles of TRIM27 in cancer and other human diseases. Firstly, we introduce the biological functions of TRIM27. Next, we focus on the roles of TRIM27 in cancer, including ovarian cancer, breast cancer and lung cancer. At the same time, we also describe the roles of TRIM27 in other human diseases, such as lupus nephritis, ischemia-reperfusion injury and Parkinson’s disease. Finally, we discuss the future directions of TRIM27 research, especially its potential roles in tumor immunity.

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