NFYB potentiates STK33 activation to promote cisplatin resistance in diffuse large B-cell lymphoma

The aberrant expression of serine/threonine kinase 33 (STK33) has been implicated in cancers. However, its clinical significance and biological functions in diffuse large B cell lymphoma (DLBCL) remain largely unknown. In the present investigation, we delineated the expression of STK33 in DLBCL and its function in cisplatin resistance.

First, genes associated with drug resistance as well as occurrence in DLBCL were analyzed by bioinformatics, followed by correlation analysis between STK33 expression and clinical baseline information of patients with DLBCL. Further, cisplatin-resistant DLBCL cell lines were constructed, and changes in cell sensitivity to cisplatin treatment were examined after interfering the expression of STK33 in parental cells as well as in drug-resistant cells, respectively. Subsequently, the downstream signaling pathways of STK33 were analyzed. Finally, the upstream regulatory mechanism of STK33 was predicted by bioinformatics as well as experimentally validated.

STK33 was overexpressed in the patients with DLBCL as well as in cisplatin-resistant DLBCL cells, and knockdown of STK33 significantly promoted sensitivity of resistant cells to cisplatin. Moreover, our further analysis revealed that STK33 promoted cisplatin resistance in DLBCL by activating the Hedgehog signaling pathway. We found in subsequent experiments that nuclear transcription factor Y subunit beta (NFYB) can bind to the STK33 promoter and thus promote STK33 expression.

The transcription factor NFYB expedites the transcription of SYK33 by binding to the STK33 promoter, thereby activating the Hedgehog signaling pathway in DLBCL cells, which in turn promotes the resistance of DLBCL cells to cisplatin.