Epigenetic events involved in organic cation transporter 1-dependent impaired response of hepatocellular carcinoma to sorafenib.

ABSTRACT:

Background and purpose

The expression of the human organic cation transporter-1 (hOCT1, gene SLC22A1) is reduced in hepatocellular carcinoma (HCC). The molecular bases of this reduction and its relationship with the poor response of HCC to sorafenib were investigated.

Experimental approach

HCC transcriptomes from 366 samples available at TCGA were analysed. Alternative splicing was determined by RT-PCR. The role of miRNAs in SLC22A1 downregulation was investigated. Expression of Oct1 was measured in rodent HCC models (spontaneously generated in Fxr^-/- mice and chemically-induced in rats). hOCT1 was overexpressed in human hepatoma cells (HuH7 and HepG2). Sorafenib and regorafenib uptake was determined by HPLC-MS/MS.

Key results

hOCT1 overexpression enhanced

SUBMITTER: Al-Abdulla R 

PROVIDER: S-EPMC6393231 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature