CircRTTN upregulates EPHA2 to aggravate the malignant process of melanoma via sponging miR-890.

BACKGROUND: Malignant melanoma is a kind of tumor derived from melanocytes, which has the characteristics of drug resistance and distant metastasis. Accumulating evidence has demonstrated that circular RNAs (circRNAs) are involved in the pathogenesis of melanoma. Our current study aimed to investigate the role and mechanism of circRTTN in melanoma progression. METHODS: The levels of circRTTN, microRNA-890 (miR-890) and EPH receptor A2 (EPHA2) were examined via quantitative real-time PCR (qRT-PCR) and Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, transwell and tube formation assays were conducted to estimate the effects of circRTTN on growth, apoptosis, migration, invasion and angiogenesis of melanoma cells. Western blot was used to measure related marker protein levels. The interaction between miR-890 and circRTTN or EPHA2 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circRTTN in vivo. RESULTS: CircRTTN and EPHA2 levels were up-regulated, while miR-890 was down-regulated in melanoma tissues and cells. CircRTTN knockdown restrained cell proliferation, migration, invasion and angiogenesis, but promoted cell apoptosis in vitro. CircRTTN was an effective molecular sponge for miR-890, and negatively regulated miR-890 expression. The suppressive role of circRTTN knockdown on cell growth, metastasis and angiogenesis in vitro was abated by blocking miR-890. MiR-890 directly targeted EPHA2. MiR-890 overexpression elicited a similar anti-tumor role in melanoma cells, which was abrogated by overexpression of EPHA2. In addition circRTTN knowdown markedly attenuated xenograft tumor growth in vivo. CONCLUSION: Our findings demonstrated that circRTTN mediated melanoma progression via regulating the miR-890/ EPHA2 axis.

Deubiquitinase BAP1 regulates stability of BRCA1 protein and inactivates the NF-κB signaling to protect mice from sepsis-induced acute kidney injury.

Sepsis and its associated organ dysfunction syndrome is a leading cause of death in critically ill patients. Breast cancer susceptibility protein 1 (BRCA1)-associated protein 1 (BAP1) is a potential regulator in immune regulation and inflammatory responses. This study aims to investigate the function of BAP1 in sepsis-induced acute kidney injury (AKI). A mouse model with sepsis-induced AKI was induced by cecal ligation and puncture, and renal tubular epithelial cells (RTECs) were treated with lipopolysaccharide (LPS) to mimic an AKI condition in vitro. BAP1 was significantly poorly expressed in the kidney tissues of model mice and the LPS-treated RTECs. Artificial upregulation of BAP1 ameliorated the pathological changes, tissue injury and inflammatory responses in kidney tissues of the mice, and it reduced the LPS-induced injury and apoptosis of the RTECs. BAP1 was found to interact with BRCA1 and enhance stability of BRCA1 protein through deubiquitination modification. Further downregulation of BRCA1 activated the nuclear factor-kappa B (NF-κB) signaling pathway and blocked the protective roles of BAP1 in sepsis-induced AKI. In conclusion, this study demonstrates that BAP1 protects mice from sepsis-induced AKI through enhancing stability of BRCA1 protein and inactivating the NF-κB signaling.