TCP10L negatively regulates alpha-fetoprotein expression in hepatocellular carcinoma

Abstract

Alpha-fetoprotein (AFP) is one of the most commonly used and reliable biomarkers for Hepatocellular carcinoma(HCC). However, the underlying mechanism of AFP expression in HCC is poorly understood. In this study, we found that TCP10L, a gene specifically expressed in the liver, is down-regulated in HCC and that its expression inversely correlates with AFP expression. Moreover, overexpression of TCP10L suppresses AFP expression whereas knockdown of TCP10L increases AFP expression, suggesting that TCP10L might be a negative regulator of AFP. We found that TCP10L is associated with the AFP promoter and inhibits AFP promoter-driven transcriptional activity. Taken together, these results indicate that TCP10L negatively regulates AFP expression in HCC and that it could be a potential prognostic marker and therapeutic target for HCC.

The Emerging Influences of Alpha-Fetoprotein in the Tumorigenesis and Progression of Hepatocellular Carcinoma

“…However, a small study in Peruvian patients with HCC demonstrated that their expression of ZHX2 was enhanced [68]. In addition, T-complex protein 10A homolog 2 (TCP10L), a new-found repressor of AFP promoter, specifically expressed in the liver and testis in normal human tissues, is down-regulated in HCC [69].…”

Whole-Genome Study of a Multigenerational Family with Essential Tremor

“…TCP10L is a primate-specific gene encoding the TCP10L protein with a subcellular localization in nuclei, 21 which was reported to be involved in transcriptional regulation and acts as a tumor suppressor. 22 Currently, the structure of TCP10L is not solved, and it is unclear how the p. Arg90Gln variant might affect protein stability. Its leucine zipper motif mediates the homodimerization of the TCP10L protein, which could be abolished in a cell culture experiment by either deletion of residues 72-108 in TCP10L or the p. Leu89Pro mutation.…”