Long noncoding RNA CCAT1 promotes cell proliferation and metastasis in human medulloblastoma via MAPK pathway.

Abstract

Medulloblastoma is the most common posterior fossa tumor in children and one that easily metastasizes. The mechanisms of how the medulloblastoma develops and progresses remain to be elucidated. The present study aimed to assess the role of long noncoding colon cancer-associated transcript-1 (lncRNA CCAT1) in cell proliferation and metastasis in human medulloblastoma. Levels of CCAT1 were measured in samples and cell lines of medulloblastoma. Cell cycle progression, cell viability assay, colony formation assay, wound-healing and Transwell assays Corning, Cambridge, MA, USA were used to investigate the viability and motility of cells. Western blot assay was used to investigate the levels of CCAT1 and other proteins. The initial findings indicated that CCAT1 was significantly up-regulated in clinical cancerous tissues and expressed differently in a series of medulloblastoma cell lines. CCAT1 knockdown significantly slowed cell proliferation rates and inhibited cell clonogenic potential in Daoy cells and D283 cells. Cell cycle progression was disrupted with cell proportions in the G0/G1 phase decreased and the proportion in the S phase and G2/M phases increased, in Daoy cells and D283 cells. Concordantly, medulloblastoma tumor cell growth rates were found to be impaired in xenotransplanted mice. After CCAT1 knockdown, cell wound recovery ability was significantly inhibited. Furthermore, the phosphorylated levels of MAPK, ERK and MEK, but not their total levels decreased after the down-regulation of CCAT1 in Daoy and D283 cells. Our results suggested that the lncRNA CCAT1 promotes cell proliferation and metastasis in human medulloblastoma by possibly regulating the MAPK pathway.