ABSTRACT
DPY30 belongs to the core subunit of components of the histone lysine methyltransferase complex, which is implicated in tumorigenesis, cell senescence, and other biological events. However, its contribution to colorectal carcinoma (CRC) progression and metastasis has yet to be elucidated. Therefore, this study aimed to investigate the biological function of DPY30 in CRC metastasis both in vitro and in vivo. Herein, our results revealed that DPY30 overexpression is significantly positively correlated with positive lymph nodes, epithelial-mesenchymal transition (EMT), and CRC metastasis. Moreover, DPY30 knockdown in HT29 and SW480 cells markedly decreased EMT progression, as well as the migratory and invasive abilities of CRC cells in vitro and lung tumor metastasis in vivo. Mechanistically, DPY30 increased histone H3K4me3 level and promoted EMT and CRC metastasis by upregulating the transcriptional expression of ZEB1. Taken together, our findings indicate that DPY30 may serve as a therapeutic target and prognostic marker for CRC.
ABSTRACT
OBJECTIVE: To study the immune tolerance induced by bone marrow cell transplantation combined with short-term use of cyclophosphamide after pancreatic transplantation in diabetic rats. METHODS: Type I diabetes mellitus was induced in BN rats with streptozotocin (STZ) intraperitoneal injection at a single dose of 45 mg/kg. Pancreatic transplantations were performed with the SD rats as donors and the diabetic BN rats as recipients. Twenty BN rats with type I diabetes mellitus were randomly divided into four groups. The BN rats in Group I received pancreas transplantations only. The BN rats in Group II received intraperitoneal injection of 150 mg/kg cyclophosphamide on the first day after pancreas transplantations. The BN rats in Group 11 received injection of 2.0 x 10(8) donors' bone marrow cells via the portal vein during the pancreas transplantations. The BN rats in Group IV received injection 2.0 x 10(8) donors' bone marrow cells via the portal vein during the pancreas transplantations and an intraperitoneal injection of 150 mg/kg cyclophosphamide on the first day after pancreas transplantations. The blood glucose of the rats was measured after transplantations. The graft functional survival time (GFST) was recorded. Peripheral blood was obtained two weeks after the transplantations to prepare single cell suspension for detecting chimera formation rate and the level of Vbeta11+ T cell by flow cytometry. RESULTS: The average GFST of group IV was (18 +/- 2.2) d, significantly longer than those of group I (7.8 +/- 1.2) d, group II (8.2 +/- 1.6) d, and group III (8.8 +/- l.4) d (P < 0.05). The rats in group IV had significant lower level of Vbeta11+ T cells (2.5 +/- 0.3)% than those in the other groups (P < 0.05). Donors' bone marrow-derived cells could be detected in the peripheral blood of diabetic rats in group IV, with a chimeric rate of (10.0 +/- 2.3)%. No donors' bone marrow-derived cells were detected in the rats in other groups. CONCLUSION: Bone marrow cell transplantation combined with short-term use of cyclophosphamide promote chimerism formation and induce immune tolerance in rats with pancreatic transplantations, which prolongs pancreatic graft functional survival time.
