Deoxycholic acid modulates the progression of gallbladder cancer through N6-methyladenosine-dependent microRNA maturation.

Oncogene
Ruirong LinJian Wang

Abstract

Bile acids (BAs), well-defined signaling molecules with diverse metabolic functions, play important roles in cellular processes associated with many cancers. As one of the most common BAs, deoxycholic acid (DCA) is originally synthesized in the liver, stored in the gallbladder, and processed in the gut. DCA plays crucial roles in various tumors; however, functions and molecular mechanisms of DCA in gallbladder cancer (GBC) still remain poorly characterized. Here, we analyzed human GBC samples and found that DCA was significantly downregulated in GBC, and reduced levels of DCA was associated with poor clinical outcome in patients with GBC. DCA treatment impeded tumor progression by halting cell proliferation. DCA decreased miR-92b-3p expression in an m6A-dependent posttranscriptional modification manner by facilitating dissociation of METTL3 from METTL3-METTL14-WTAP complex, which increased the protein level of the phosphatase and tensin homolog, a newly identified target of miR-92b-3p, and subsequently inactivated the PI3K/AKT signaling pathway. Our findings revealed that DCA might function as a tumor suppressive factor in GBC at least by interfering with miR-92b-3p maturation, and suggested that DCA treatment could provide a n...Continue Reading

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Citations

Apr 22, 2021·Biomarker Research·Yiqing CaiXin Wang
Jun 15, 2021·Frontiers in Cell and Developmental Biology·Shuai LiuZhilong Dong

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Methods Mentioned

BETA
surgical resection
xenograft
PCR
immunoprecipitation
thermal shift
co-immunoprecipitation
transfection
RNA-seq
Hi-Seq
electrophoresis

Software Mentioned

Meier plotter
Kaplan
SPSS
DARTS
DESeq2
R Bioconductor

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