CAMKII? is a targetable driver of multiple myeloma through CaMKII?/ Stat3 axis.

ABSTRACT: Aberrant activation of CAMKII? has been linked to leukemia and T-cell lymphoma, but not multiple myeloma (MM). The purpose of this study was to explore the role of CaMKII? in the pathogenesis and therapy of MM. In this study, we found that CaMKII? was aberrantly activated in human MM and its expression level was positively correlated with malignant progression and poor prognosis. Ectopic expression of CaMKII? promoted cell growth, colony formation, cell cycle progress and inhibited apoptosis of MM cell lines, whereas, knockdown of CAMKII? expression suppressed MM cell growth in vitro and in vivo. Mechanically, we observed that CaMKII? overexpression upregulated p-ERK and p-Stat3 levels and suppression of CaMKII? had opposite effects. CaMKII? is frequently dysregulated in MM and plays a critical role in maintaining MM cell growth through upregulating STAT3 signaling pathway. Furthermore, our preclinical studies suggest that CaMKII? is a potential therapeutic target in MM, and could be intervened pharmacologically by small-molecule berbamine analogues.

SUBMITTER: Yang L 

PROVIDER: S-EPMC7377902 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature