A preliminary study on the mechanism of VASH2 in childhood medulloblastoma

Abstract

Abstract Objective: To investigate the difference in VASH2 expression in tumor tissues of different molecular subtypes of pediatric medulloblastoma (MB), to analyze the correlation between VASH2 and molecular subtypes of medulloblastoma, clinicopathological data, and prognosis, and to explore the mechanism of VASH2's role in pediatric medulloblastoma. Methods: We analyzed 47 pediatric medulloblastoma cases treated in the Department of Pediatric Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University between January 2011 and December 2019, and detected the expression levels of YAP1 and GAB1 in these tumor tissues using immunohistochemistry (IHC), and performed molecular typing (WNT-type, SHH-type, non-WNT-type/SHH-type). To analyze the correlation between VASH2 and molecular subtypes of medulloblastoma. We focused on vasopressor 2 (VASH2) and investigated its biological role in DAOY cell proliferation, apoptosis, migration, invasion, and with the cell cycle by overexpressing and knocking down VASH2 in the medulloblastoma cell line DAOY, respectively, in vitro by small interfering RNA technology. Results: 1. Among 47 pediatric medulloblastoma cases, 8 were WNT type, 29 were SHH type, and 10 were non-WNT/SHH type. the positive rate of VASH2 was highest in the SHH type with a 68.97% positive rate, followed by non-WNT/SHH and lowest in the WNT type. The results of the multifactorial analysis showed that positive expression of VASH2 was associated with medulloblastoma molecular subtype (SHH type), site of tumor development (four ventricles), and gender (male), P < 0.05.2 The results of cellular experiments showed that overexpression of VASH2 increased the invasion and migration ability of medulloblast Daoy, while knockdown of VASH2 inhibited the invasion and Overexpression of VASH2 upregulated the expression of Smad2+3, Smad4, Mmp2 and the apoptotic indicators Bcl-2 and Caspase3, while knockdown of VASH2 suppressed the expression of Smad2+3 and Mmp2, and silenced the expression of Smad4 and the apoptotic indicators Bcl2, Caspase3 expression. Flow cytometric cycle analysis showed that VASH2 overexpression increased the S phase in the Daoy cell cycle, while VASH2 knockdown decreased the S phase in the Daoy cell cycle. Conclusion: We found for the first time that the positive expression rate of VASH2 was closely associated with SHH-type pediatric medulloblastoma, and VASH2 was involved in the invasion, migration, cell cycle, and apoptotic ability of the medulloblast cell line DAOY by affecting downstream indicators of the TGF-β pathway. It is suggested that it is involved in the progression of childhood medulloblastoma, and VASH2 is expected to be a diagnostic and therapeutic target for SHH-type childhood medulloblastoma.