Dihydroartemisinin represses oral squamous cell carcinoma progression through downregulating mitochondrial calcium uniporter

Dysregulation of mitochondrial calcium uniporter (MCU) exerts a carcinogenic effect in several cancers. Nevertheless, the roles of MCU in oral squamous cell carcinoma (OSCC) remain elusive. It has been reported that dihydroartemisinin (DHA) may suppress the progression of OSCC but its associated mechanisms have not been investigated. The purpose of our research was to observe the biological function of MCU on OSCC and its regulatory relationship with DHA. MCU, MICU1, MICU2, N-cadherin, TGF-beta and vimentin expression was detected in OSCC and peritumoral tissues by immunohistochemistry and Western blot. Following DHA treatment, the expression of the aforementioned proteins was detected in CAL-27 cells transfected with shMCU or pcDNA3.1-MCU by Western blot or immunofluorescence. Furthermore, clone formation, mitochondrial membrane potential (MMP), wound healing and transwell assays were presented in CAL-27 cells treated with DHA, shMCU or pcDNA3.1-MCU. Our results showed that the members of MCU complex (MCU, MICU1 and MICU2) were overexpressed in OSCC than peritumoral tissues. Furthermore, TGF-beta and epithelial to mesenchymal transition (EMT) proteins (N-cadherin and vimentin) exhibited higher expression in OSCC. DHA treatment significantly lowered the expression of MCU in CAL-27 cells. MCU overexpression reversed the inhibitory effects of DHA on MICU1, MICU2, N-cadherin, TGF-beta and vimentin. MCU knockdown or DHA suppressed proliferation, MMP and migration of CAL-27 cells. DHA treatment could reverse the effects of MCU overexpression. Collectively, our study demonstrated that MCU was an oncogene of OSCC and DHA exerted a suppressive role on proliferation and migration of OSCC cells by suppressing MCU expression.

Automated summary

Dysregulation of mitochondrial calcium uniporter (MCU) plays a carcinogenic role in several cancers, including oral squamous cell carcinoma (OSCC). The study aimed to investigate the role of MCU in OSCC and its regulatory relationship with dihydroartemisinin (DHA). The results showed that MCU and its complex members were overexpressed in OSCC and DHA treatment suppressed MCU expression. MCU overexpression reversed the inhibitory effects of DHA on other proteins. Knockdown of MCU or DHA treatment suppressed proliferation and migration of OSCC cells.