Mitochondrial Calcium Uniporter (MCU) that Modulates Mitochondrial Calcium Uptake and Facilitates Endometrial Cancer Progression through Interaction with VDAC1.

BACKGROUND: Although endometrial cancer represents a frequently diagnosed malignancy of the female reproductive tract, we know very little about the factors that control endometrial cancer. OBJECTIVE: Our study was presented to investigate the function of MCU in endometrial tumorigenesis and the molecular mechanisms involved. MATERIALS AND METHODS: A total of 94 endometrial cancer patients were recruited into our cohort. MCU and VDAC1 expression was examined in tumor and normal tissues via immunohistochemistry and immunofluorescence. Associations of MCU and VDAC1 expression with clinicopathological characteristics were evaluated. After transfection with shRNA targeting MCU or full-length MCU plasmids, clone formation, wound healing, transwell and MitoTracker Red staining were separately presented in Ishikawa and RL95-2 cells. Moreover, Western blotting or immunofluorescence was utilized to examine the expression of MCU, VDAC1, Na+/Ca2+/Li+ exchanger (NCLX), and ß-catenin under VDAC1 knockdown and/or MCU overexpression or knockdown. RESULTS: MCU and VDAC1 expression were prominently up-regulated in endometrial cancer tissues and were significantly associated with histological grade, depth of myometrial invasion and lymph node status. MCU up-regulation enhanced clone formation, migration, and mitochondrial activity of endometrial cancer cells. The opposite results were investigated when MCU was silenced. MCU or VDAC1 silencing reduced the expression of MCU, VDAC1, NCLX, and ß-catenin. Moreover, VDAC1 knockdown alleviated the promoting effect of MCU overexpression on the above proteins. CONCLUSION: This investigation demonstrated that MCU-induced mitochondrial calcium uptake plays a critical role in endometrial tumorigenesis through interaction with VDAC1.

Adenosine Receptor A2B Antagonist Inhibits the Metastasis of Gastric Cancer Cells and Enhances the Efficacy of Cisplatin.

Adenosine receptors play a key role in cancer progression. This study investigated the effect of the adenosine A2B receptor (ADORA2B) on epithelial-mesenchymal transition (EMT) markers and cell metastasis of gastric cancer (GC) cells. Public databases were used to investigate the specificity of ADORA2B expression in GC tissue. We used immunohistochemistry and immunofluorescence to detect ADORA2B expression in GC tissue, paracancerous tissue, and metastatic greater omental tissue. AGS and HGC-27 GC cells were selected. The effect of ADORA2B on the invasion and migration of GC cells was examined using cell scratch and transwell assays. The effect of ADORA2B on the expression of EMT marker proteins (ß-catenin, N-cadherin, and vimentin) in GC cells was measured by cellular immunohistochemistry, immunofluorescence, and Western blot. The effects of an ADORA2B inhibitor combined with cisplatin on EMT markers in GC cells were further explored. The expression levels of ADORA2B in GC tissue, metastatic greater omental tissue, and lymphatic metastasis tissue were significantly higher than those in paracancerous tissue, and ADORA2B was associated with lymph node metastasis and invasion. ADORA2B significantly regulated the invasion and migration ability of GC cells and the expression levels of EMT marker proteins. The combination of an ADORA2B antagonist (PSB-603) and cisplatin had a more significant effect on reversing the expression of EMT marker proteins. ADORA2B was overexpressed in GC tissue, metastatic greater omental tissue, and metastatic lymph node tissue. ADORA2B regulated the expression of EMT marker proteins in GC cells and affected GC cell metastasis. Antagonizing ADORA2B expression increased the efficacy of cisplatin treatment.

Attenuated SUMOylation of sirtuin 1 in premature neonates with bronchopulmonary dysplasia.

A prospective study was performed to investigate the effects of hyperoxia on the expression of small ubiquitin­related modifier (SUMO) and sirtuin 1 (SIRT1) proteins, and to examine interactions between these proteins in premature neonates with bronchopulmonary dysplasia (BPD). Peripheral blood mononuclear cells (PBMCs) were isolated from residual venous blood samples of 20 premature infants with BPD and 20 gender­matched premature infants without BPD (non­BPD group). Expression levels of SUMO and SIRT1 proteins in PBMCs were assessed by western blot analysis, and their interactions in PBMCs were detected using the immunoprecipitation assay. Based on the fraction of inspired oxygen (FiO2) administered, neonates were divided into normoxia, low­(21%

[Decreased SIRT1 expression is related to bronchopulmonary dysplasia in premature infants after oxygen exposure].

Objective To observe silent information regulator 1 (SIRT1) expression in the peripheral blood mononuclear cells (PBMCs), and explore the relationship between SIRT1 expression and bronchopulmonary dysplasia (BPD) in premature infants after oxygen exposure. Methods Premature infants with 28 to 30 weeks' gestation were divided into three groups according to the fraction of inspiration O2 (FiO2): low-oxygen group with FiO2<30%, medium-oxygen group with FiO2 being 30%~40%, and high-oxygen group with FiO2≥40%; other premature infants with 28 to 30 weeks' gestation and without inspiration O2 served as a control group. The children's clinical data and residual blood samples obtained from the routine examination of 0, 7, 14 and 28 days of hospitalization were collected, and PBMCs were isolated and cryopreserved in -80DegreesCelsius refrigerator. Twenty children diagnosed with BPD were enrolled as a BPD group, and other sex-matched 20 children without BPD were randomly chosen as a non-BPD group. The children's clinical data were retrospectively analyzed, and SIRT1 expression in the PBMCs of each group was measured by Western blotting. Furthermore, the role of SIRT1 expression in the occurrence and development of BPD in premature infants was also analyzed. Results Compared with the control group, SIRT1 expression in the medium-oxygen group and the high-oxygen group significantly decreased with the increase of FiO2, and the expression in the low-oxygen group and the control group was almost at a similar level. Compared with the non-BPD group, SIRT1 expression in the BPD group of 14 and 28 days was significantly reduced. Conclusion There is a certain relationship between the decreased SIRT1 expression in PBMCs and the occurrence of BPD in premature infants after continuous and high-concentration oxygen exposure.