Department of Orthodontics and Prosthodontics, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, China.
Department of Stomatology, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, China.
Bioengineered. 2022 Jan;13(1):227-241. doi: 10.1080/21655979.2021.2012951.
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-β 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-β 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-β 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.
线粒体钙单向转运体（MCU）的失调对几种癌症具有致癌作用。然而，MCU 在口腔鳞状细胞癌（OSCC）中的作用仍不清楚。有报道称二氢青蒿素（DHA）可能抑制 OSCC 的进展，但尚未研究其相关机制。我们的研究目的是观察 MCU 在 OSCC 中的生物学功能及其与 DHA 的调节关系。通过免疫组织化学和 Western blot 检测 OSCC 和癌旁组织中 MCU、MICU1、MICU2、N-钙粘蛋白、TGF-β 和波形蛋白的表达。DHA 处理后，通过 Western blot 或免疫荧光检测转染 shMCU 或 pcDNA3.1-MCU 的 CAL-27 细胞中上述蛋白的表达。此外，在 DHA、shMCU 或 pcDNA3.1-MCU 处理的 CAL-27 细胞中进行克隆形成、线粒体膜电位（MMP）、划痕愈合和 Transwell 测定。结果表明，MCU 复合物（MCU、MICU1 和 MICU2）成员在 OSCC 中的表达高于癌旁组织。此外，TGF-β 和上皮间质转化（EMT）蛋白（N-钙粘蛋白和波形蛋白）在 OSCC 中表达更高。DHA 处理显著降低了 CAL-27 细胞中 MCU 的表达。MCU 过表达逆转了 DHA 对 MICU1、MICU2、N-钙粘蛋白、TGF-β 和波形蛋白的抑制作用。MCU 敲低或 DHA 抑制 CAL-27 细胞的增殖、MMP 和迁移。DHA 处理可逆转 MCU 过表达的作用。总之，我们的研究表明，MCU 是 OSCC 的癌基因，DHA 通过抑制 MCU 表达对 OSCC 细胞的增殖和迁移发挥抑制作用。
