RNA-seq for HepG2 cell line with AUF1 knockdown.

ABSTRACT: Although several studies indicate that ARE-specific RNA binding proteins (ARE-BPs) contribute to the development of cancer, the detailed functions and mechanisms of ARE-BPs have not been fully elucidated. By using a bioinformatics analysis of two well-established hepatocellular carcinoma (HCC) datasets, we identified the AU-rich binding factor 1(AUF1), one of the well-known ARE-BPs, was abnormally highly expressed in HCC and the high expression of AUF1 was correlated with poor prognosis of HCC patients. The prognostic value of AUF1 expression was also confirmed in our HBV-related HCC cohorts. Gain and loss of function analyses demonstrated that AUF1 promoted HCC tumorigenesis both in vitro and in vivo. Mechanistically, we found that aldoketo reductase family 1 member B 10(AKR1B10) was a critical target of AUF1 and was essential for sustaining the AUF1-induced proliferation of HCC cells. AUF1 stabilized AKR1B10 mRNA by binding to the 3'UTR region of AKR1B10. Additionally, we confirmed that E2F1 enhanced AUF1 expression in HCC through the transcription level, and in HBV-related HCC, HBx could up-regulate E2F1 expression and promote the expression of AUF1. Our study reveals a novel role of AUF1 in promoting hepatocarcinogenesis via the post-transcriptional regulation of AKR1B10 expression and proposes that the HBx/E2F1/AUF1/AKR1B10 pathway may serve as a potential therapeutic target in HCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162706 | GEO | 2021/05/01

REPOSITORIES: GEO