This study is to explore the mechanism of KDM1A-regulated hepatoblastoma (HB) development. Cancerous and paracancer tissues of 30 HB patients were collected for detection of KDM1A and DKK3 expression. HuH-6 and HepG2 cells were subjected to assays of cellular activities after treatment with sh-KDM1A, sh-DKK3, and/or XAV-939 (an inhibitor of the Wnt/β-catenin pathway). Chromatin immunoprecipitation was used to determine the interaction of KDM1A with DKK3. Nude mice were injected with HuH-6 cells in which KDM1A was knocked down. KDM1A was highly expressed and DKK3 was lowly expressed in HB patients. Knockdown of KDM1A reduced the proliferative and invasive capabilities of HepG2 and HuH-6 cells and accelerated the cell apoptosis; these influences were nullified by knockdown of DKK3. KDM1A inhibited DKK3 transcription by reducing H3 methylation. XAV-939 treatment inhibited the development of HepG2 and HuH-6 cells in which KDM1A and DKK3 were both knocked down. Knockdown of KDM1A reduced the tumor mass, inactivated the Wnt/β-catenin signaling, and increased the expression of DKK3 in nude mice. KDM1A stimulates HB development by activating the Wnt/β-catenin pathway through inhibition of DKK3 transcription.
Keywords: DKK3; Hepatoblastoma; KDM1A; Wnt/β-catenin.
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