Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up‐regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up‐regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock‐down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR‐29a‐3p sponge to up‐regulate SLC25A15 expression by bioinformatics analysis, dual‐luciferase reporter assays and biotinylated RNA pull‐down assays. SLC25A15 could reverse the tumour suppressing roles of knock‐down circFOXO3 in PCa. Of note, we found that miR‐29a‐3p was down‐regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR‐29a‐3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up‐regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.

Tim-4 is expressed primarily on APCs, including macrophages, and has been shown to play a critical role in T cell regulation. However, it remains unclear whether Tim-4 also plays a role in the regulation of macrophage functions. In the present study, we investigated the effects of Tim-4 on macrophage activity in Con A-induced hepatitis in mice. We found that high levels of Tim-4 expression were associated with a diminished serum level of ALT in Con A-induced hepatitis. In addition, adoptive transfer of T4-RAW cells resulted in a significant decrease in ALT levels and Con A-induced liver injuries in mice. Concurrently, T4-RAW cells transfer displayed, markedly decreased apoptosis in liver and depressed TNF-alpha secretion in serum, supporting the hypothesis that Tim-4 protects Con A-induced hepatitis by negatively regulating macrophages. Consistent with the in vivo findings, in vitro studies showed that Tim-4 overexpression in RAW264.7 cells was associated with decreased expression of CD80, CD86, and MHCII molecules and the production of TNF-alpha. Moreover, Tim-4 blockade promoted LPS-induced macrophage activation. In conclusion, these findings indicate that Tim-4 plays an important role in alleviating liver damage by inhibition of macrophage activity. Tim-4 pathway could be a potential target for the treatment of acute hepatitis.

Enhanced chemoresistance is, among other factors, believed to be responsible for treatment failure and tumor relapse in patients with epithelial ovarian cancer (EOC). Here, we exposed EOC cells to interleukin-6 (IL-6) to activate oncogenic STAT3, which directly repressed miR-204 via a conserved STAT3-binding site near the TRPM3 promoter region upstream of miR-204. Repression of miR-204 was required for IL-6-induced cisplatin (cDDP) resistance. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a direct miR-204 target. Importantly, the resulting IL-6R/STAT3/miR-204 feedback loop was identified in patients with EOC, and its activity correlated with chemosensitivity. Moreover, exogenous miR-204 blocked this circuit and enhanced cDDP sensitivity both in vitro and in vivo by inactivating IL-6R/STAT3 signaling and subsequently decreasing the expression of anti-apoptotic proteins. Our findings illustrate the function of this feedback loop in cDDP-based therapy and may offer a broadly useful approach to improve EOC therapy.

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The hepatitis B virus core protein (HBc), also named core antigen, is well-known for its key role in viral capsid formation and virus replication. Recently, studies showed that HBc has the potential to control cell biology activity by regulating host gene expression. Here, we utilized miRNA microarray to identify 24 upregulated miRNAs and 21 downregulated miRNAs in HBc-expressed HCC cells, which were involved in multiple biological processes, including cell motility. Consistently, the in vitro transwell assay and the in vivo tail-vein injection model showed HBc promotion on HCC metastasis. Further, the miRNA-target gene network analysis displayed that the deleted in liver cancer (DLC-1) gene, an important negative regulator for cell motility, was potentially targeted by several differentially expressed miRNAs in HBc-introduced cells. Introduction of miRNAs mimics or inhibitors and 3'UTR luciferase activity assay proved that miR-382-5p efficiently suppressed DLC-1 expression and its 3'-UTR luciferase reporter activity. Importantly, cotransfection of miR-382-5p mimics/inhibitors and the DLC-1 expression vector almost abrogated HBc promotion on cell motility, indicating that the miR-382-5p/DLC-1 axis is important for mediating HBc-enhanced HCC motility. Clinical HCC samples also showed a negative correlation between miR-382-5p and DLC-1 expression level. Furthermore, HBc-positive HCC tissues showed high miR-382-5p level and reduced DLC-1 expression. In conclusion, our findings revealed that HBc promoted HCC motility by regulating the miR-382-5p/DLC-1 axis, which might provide a novel target for clinical diagnosis and treatment.