lncRNA PCAT-1 interacting with FZD6 contributes to the malignancy of acute myeloid leukemia cells through activating Wnt/β-catenin signaling pathway

Am J Transl Res. 2019 Nov 15;11(11):7104-7114. eCollection 2019.

Abstract

Accumulating evidence has suggested the involvement of long noncoding RNAs (lncRNAs) on the acute myeloid leukemia (AML). Therefore, this study aimed to investigate the unknown function of lncRNA Prostate cancer-associated transcript-1 (PCAT-1) in AML cells. Our data found that PCAT-1 was highly expressed in AML-M1/2 and AML-M3 patients than normal controls and its expression was significantly up-regulated in AML cell lines Kasumi-6 and HL-60. The functional experiments demonstrated that knockdown of PCAT-1 remarkably inhibited proliferation, arrested cell cycle progression and triggered apoptosis of AML cells. Mechanistically, we revealed that PCAT-1 could directly interact with FZD6 protein to regulate its stability. Overexpression of FZD6 partly abolished the effects of PCAT-1 silencing on AML cells. Our integrated experiments then suggested that PCAT-1 could activate the Wnt/β-catenin signaling pathway in an FZD6-dependent manner. Taken together, the present study indicated that PCAT-1 interacting with FZD6 to activate Wnt/β-catenin signaling, which may play an important role in the pathogenesis of AML.

Keywords: Acute myeloid leukemia; FZD6; PCAT-1; Wnt/β-catenin signaling.