Integrated Bioinformatic Investigation of EXOSCs in Hepatocellular Carcinoma Followed by the Preliminary Validation of EXOSC5 in Cell Proliferation

The Exosome complex (EXOSC) is a multiprotein complex that was originally discovered as the machinery of RNA degradation. Interestingly, recent studies have reported that EXOSC family members (EXOSCs) are associated with various human diseases, including cancers. It will be interesting to investigate whether EXOSCs are related to the processes of hepatocellular carcinoma (HCC). In this study, multiple public databases and experimental validation were utilized to systemically investigate the role of EXOSCs, especially EXOSC5, in HCC. It is worth considering that the mRNA and protein levels of many EXOSCs were elevated in HCC, although there were some differences in the results from different database analyses. The over-expression of EXOSCs could predict HCC to some extent, as evidenced by the positive correlation between the elevated EXOSCs and alpha fetoprotein (AFP) levels, as well as with a high accuracy, as shown by the receiver operating characteristic curve analysis. Additionally, higher mRNA expressions of specific EXOSCs were significantly related to clinical cancer stage, shorter overall survival and disease-free survival in HCC patients. A moderate mutation rate of EXOSCs was also observed in HCC. Furthermore, a gene functional enrichment analysis indicated that EXOSCs were mainly involved in the metabolism of RNA. Moreover, we revealed that the expression of EXOSCs is remarkably related to immune cell infiltration. Finally, EXOSC5 was upregulated in HCC tissues and cell lines, promoting cell growth and proliferation via activated signal transducer and activator of transcription 3 (STAT3). The bioinformatic analyses, following verification in situ and in vitro, provided a direction for further functions and underlying mechanism of EXOSCs in HCC.

Automated summary

In this study, the role of EXOSCs, especially EXOSC5, in hepatocellular carcinoma (HCC) was systematically investigated using multiple public databases and experimental validation. It was found that EXOSCs were elevated in HCC and their over-expression could predict HCC to some extent. Higher mRNA expressions of specific EXOSCs were related to clinical cancer stage, shorter overall survival and disease-free survival in HCC patients. Bioinformatic analyses also revealed the involvement of EXOSCs in RNA metabolism and immune cell infiltration. Additionally, it was discovered that EXOSC5 promoted cell growth and proliferation in HCC via activated STAT3.