Circular RNAs (circRNAs) are a new type of non-coding RNAs and their functions in gastric cancer (GC) remain unclear. Recent studies have revealed that circRNAs play an important role in cancer development and certain types of pathological responses, acting as microRNA (miRNA) sponges to regulate gene expression. CircNet was used to screen potential circRNAs and validated circYAP1 expression levels in 17 GC tissues by quantitative real-time PCR (qRT-PCR) and another 80 paired GC tissues by FISH. CircYAP1 overexpression and knockdown experiments were conducted to assess the effects of circYAP1 in vitro and in vivo, and its molecular mechanism was demonstrated by RNA in vivo precipitation assays, western blotting, luciferase assay and rescue experiments. CircYAP1 expression level was significantly lower in GC tissues than the adjacent normal tissues, and GC patients with circYAP1 low expression had shorter survival times as compared with those with circYAP1 high expression. Functionally, circYAP1 overexpression inhibited cell growth and invasion in vitro and in vivo, but its knockdown reversed these effects. Further analysis showed that circYAP1 sponged miR-367-5p to inhibit p27 Kip1 expression and GC progression. Our findings demonstrate that circYAP1 functions as a tumor suppressor in GC cells by targeting the miR-367-5p/p27 Kip1 axis and may provide a prognostic indicator of survival in GC patients.

To investigate the role of nuclear division cycle (NDC)80 in human hepatocellular carcinogenesis. NDC80 gene expression was analyzed by real-time reverse transcription polymerase chain reaction in 47 paired hepatocellular carcinoma (HCC) and adjacent tissues. The HCC cell line SMMC-7721 was transfected with lentivirus to silence endogenous NDC80 gene expression, which was confirmed by real-time polymerase chain reaction and western blotting. The effects of NDC80 silencing on SMMC-7721 cell proliferation were evaluated by Cellomics ArrayScan VTI imaging. Cell cycle analysis and apoptosis were detected with flow cytometry. Colony formation was assessed by fluorescence microscopy. NDC80 expression levels in HCC tissues were significantly higher than those in the adjacent tissues. Functional studies demonstrated that NDC80 silencing significantly reduced SMMC-7721 cell proliferation and colony formation. Knockdown of NDC80 resulted in increased apoptosis and cell cycle arrest at S-phase. NDC80 contributed to HCC progression by reducing apoptosis and overcoming cell cycle arrest. Elevated expression of NDC80 may play a role in promoting the development of HCC.

Non-alcoholic fatty liver disease (NAFLD) is characterized by increased uptake and accumulation of lipids in hepatocytes. Simple steatosis may progress to non-alcoholic steatohepatitis (NASH) with inflammation, hepatocellular injury and fibrosis. CCN1 is an important matrix protein that regulates cell death and promotes immune cell adhesion and may potentially control this process. The role of CCN1 in NASH remains unclear. We investigated the role of CCN1 in the pathogenesis of steatohepatitis. CCN1 upregulation was found to be closely related with steatosis in patients with NASH, obese mice and a FFA-treated hepatocyte model. Controlling the expression of CCN1 in murine NASH models demonstrated that CCN1 increased the severity of steatosis and inflammation. From the sequence results, we found that fatty acid metabolism genes were primarily involved in the MCD mice overexpressing CCN1 compared to the control. Then, the expression of fatty acid metabolism genes was determined using a custom-designed pathway-focused qPCR-based gene expression array. Expression analysis showed that CCN1 overexpression significantly upregulated the expression of fatty acid metabolism-associated genes. In vitro analysis revealed that CCN1 increased the intracellular TG content, the pro-inflammatory cytokines and the expression level of apoptosis-associated proteins in a steatosis model using murine primary hepatocytes. We identified CCN1 as an important positive regulator in NASH.