Background Long non-coding RNAs (lncRNAs) have been proved to play a vital role in pancreatic cancer (PC). However, the role of lncRNA FAM83A-AS1 in PC remains unclear. In this study, we explored the biological function and underlying mechanism of FAM83A-AS1 in PC cells.Methods The FAM83A-AS1 expression was assessed via public databases and validated by qRT-PCR. The biofunction and immune cell infiltration of FAM83A-AS1 were analyzed through GO, KEGG, GESA and ssGSEA. The migration, invasion and proliferation abilities of PC cells were examined by Transwell, wound healing, CCK8 and colony formation. The EMT and Hippo pathway markers were evaluated by western blot.Results FAM83A-AS1 expression was higher in PC tissues and cells than normal. Additionally, FAM83A-AS1 was associated with poor prognosis of PC and involved in cadherin binding and immune infiltration. Subsequently, we proved FAM83A-AS1 overexpression enhanced the migration, invasion and proliferation abilities of PC cells, whereas FAM83A-AS1 downregulation inhibited those. Moreover, western blot results showed that FAM83A-AS1 knockdown increased the E-cadherin expression and decreased the expression of N-cadherin, β-catenin, Vimentin, Snail and Slug. On the contrary, FAM83A-AS1 upregulation results in the opposite effects. Besides, FAM83A-AS1 overexpression inhibited the expression of p-YAP, p-MOB1, p-Lats1, SAV1, MST1 and MST2 as well as the results of FAM83A-AS1 knockdown were opposite.Conclusion FAM83A-AS1 promoted EMT of PC cells via Hippo signaling inactivation and may be a potential diagnosis and prognosis target.
Two-dimensional sheet-like nanomaterial molybdenum disulfide (MoS 2 ) has extensive potential applications in the biomedical field. Nevertheless, upon entering the body, MoS 2 tends to accumulate markedly in the liver, drawing increasing attention to its potential hepatotoxicity. In this study, we demonstrated that MoS 2 nanosheets exerted cytotoxic effects on the liver both in vitro and in vivo . Further exploration of the toxicity mechanism, utilizing genome-wide CRISPR-Cas9 screening and molecular biological techniques, uncovered that MST2 protein is crucial in mediating MoS 2 -induced cytotoxicity. Moreover, protein mass spectrometry and molecular dynamics simulation results indicated that MoS 2 directly binds to MST2 protein, thereby promoting its phosphorylation and activation. Subsequently, phosphorylated MST2 protein activates the Hippo signaling pathway, which in turn suppresses liver cell proliferation. Our in vivo experiments revealed that MST2 is indispensable for MoS 2 -induced impairment of liver regeneration in mice and disordered liver development in zebrafish. Meanwhile, the MoS 2 /MST2 axis was to found induce hepatocyte death via activation of autophagy dependent on LC3 protein. Collectively, this study provides a foundation for a comprehensive understanding of the biological behavior and hepatotoxicity of MoS 2 , offering valuable insights for the safety assessment of nanomaterials and the rational design of future nanomedicines.
危险品化学品经营许可证（带存储）