Profilin 1 and its role in proteasome inhibitors resistance

Browsing through the most recent proteomics dataset on the public PRIDE database, I came across this study (PXD033148) from Wang and colleagues  at Xiangya Hospital of Central South University in China. In this study, they overexpressed Profilin 1 (PFN1), a protein that has been implicated in metastasis and drug resistance in cancer, in H1299 cells.

I decided to upload the dataset on the Omics Playground platform and look at the differences between cells overexpressing PFN1 and empty vector controls. The GSE analysis module revealed a striking negative correlation between PFN1 overexpression and gene sets associated with the proteasome (Fig.1, highlighted in blue).

Figure 1. Most negatively correlated expression profiles. Highlighted in blue are proteasome-related genesets, highlighted in red are proteasome inhibitor profiles.

As it happens, the same group recently published an article implicating PFN1 over-expression at the transcriptome level with bortezomib resistance in multiple myeloma. It is thus interesting to observe that  the overexpression of PFN1 induces a protein expression pattern that is strongly opposed not only to the profile generated by bortezomib, but also that of a different proteasome inhibitor, carfilzomib (Fig.1, highlighted in red). In particular, PFN1 overexpression appears to inhibit the expression of most of the subunits of the proteasome S20 particle (Fig. 2), which also happens to be the binding target of carfilzomib. 

Figure 2. Differentially expressed proteins in the KEGG proteasome pathway following PFN1 overexpression. Proteins in blue are downregulated, proteins in red upregulated.

The data was produced as part of the following published study: https://doi.org/10.3389/fphar.2022.890891.

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