ABSTRACT
Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long noncoding RNA (lncRNA) that is widely expressed in a variety of mammalian cell types. Altered expression levels of the lncRNA NEAT1 have been reported in liver-related disorders including cancer, fatty liver disease, liver fibrosis, viral hepatitis, and hepatic ischemia. lncRNA NEAT1 mostly acts as a competing endogenous RNA (ceRNA) to sponge various miRNAs (miRs) to regulate different functions. In regard to hepatic cancers, the elevated expression of NEAT1 has been reported to have a relation with the proliferation, migration, angiogenesis, apoptosis, as well as epithelial-mesenchymal transition (EMT) of cancer cells. Furthermore, NEAT1 upregulation has contributed to the pathogenesis of other liver diseases such as fibrosis. In this review, we summarize and discuss the molecular mechanisms by which NEAT1 contributes to liver-related disorders including acute liver failure, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and liver carcinoma, providing novel insights and introducing NEAT1 as a potential therapeutic target in these diseases.
Subject(s)
MicroRNAs , Non-alcoholic Fatty Liver Disease , RNA, Long Noncoding , Animals , Humans , Cell Proliferation/genetics , Fibrosis , Liver Cirrhosis/genetics , Mammals/genetics , Mammals/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Non-alcoholic Fatty Liver Disease/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
BACKGROUND: Delivery systems with low immunogenicity and toxicity are believed to enhance the efficacy of specific targeted drug delivery to cancer cells. Exosomes are potential natural nanosystems that can enhance the delivery of therapeutic agents for targeted cancer therapy. OBJECTIVE: This study provides a precise effect size of exosomes as nanovesicles for in vitro delivery of anticancer agents. METHODS: In this systematic review and meta-analysis, the efficacy of exosomes as nanocarriers for the delivery of therapeutic molecules was investigated using the random-effects model. We did comprehensive literature searches through CINAHL, Cochrane, PubMed, Scopus, and Science Direct of in vitro studies that reported exosomes as delivery systems for cancer therapy. RESULTS: After the screening of eligible articles, a total of 50 studies were enrolled for the metaanalysis. The results showed that cancer cells treated with exosome-loaded anticancer agents for at least 6 h significantly decreased cell viability and increased cytotoxicity with the standardized mean difference (SMD) of -1.47 (-2.18, -0.76; (p<0.0001) and -1.66 (-2.71, -0.61; p<0.002). Exosomes effectively delivered drugs and exogenous miRNAs, siRNAs, viruses, and enzymes to cancer cells in vitro. CONCLUSION: This meta-analysis provides evidence of exosomes as efficient nanocarriers for the delivery of anticancer drugs.
