IE86 Inhibits the apoptosis and promotes the cell proliferation of glioma cells via the hnRNP A2/B1-mediated alternative splicing of Bcl-x.

Human cytomegalovirus (HCMV), a ubiquitous pathogen, can cause severe illness in immunocompromised individuals. Typically, glioma is one of the most common malignant primary brain tumors and originates in the central nervous system. The IE86 gene of HCMV exerts a major role in regulating virus replication. By using coimmunoprecipitation combined with mass spectrometry, the components of the IE86 complex were identified, and the heterogeneous ribonucleoprotein A2/B1 (hnRNP A2/B1) was recognized as one of the IE86 complex components. hnRNP A2/B1 is highly expressed in U251 cells, and the data suggest that IE86 can promote hnRNP A2/B1 expression. Furthermore, the knockdown of hnRNP A2/B1 significantly attenuates IE86-mediated apoptosis and cell proliferation. Importantly, IE86 can also inhibit the alternative splicing of Bcl-x by decreasing the Bcl-xS/Bcl-xL ratio, which is closely related to apoptosis. Meanwhile, the knockdown of hnRNP A2/B1 can mitigate the inhibitory effect of IE86 on the alternative splicing of Bcl-x. In conclusion, the inhibition of apoptosis and enhancement of cell proliferation by IE86 may be related to the hnRNP A2/B1-mediated alternative splicing of Bcl-x.