The Good, the Bad, the Question-H19 in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is challenging to treat due to its typical late diagnosis, mostly at an advanced stage. Therefore, there is a particular need for research in diagnostic and prognostic biomarkers and therapeutic targets for HCC. The use of long noncoding (lnc) RNAs can widen the list of novel molecular targets improving cancer therapy. In hepatocarcinogenesis, the role of the lncRNA H19, which has been known for more than 30 years now, is still controversially discussed. H19 was described to work either as a tumor suppressor in vitro and in vivo, or to have oncogenic features. This review attempts to survey the conflicting study results and tries to elucidate the potential reasons for the contrary findings, i.e., different methods, models, or readout parameters. This review encompasses in vitro and in vivo models as well as studies on human patient samples. Although the function of H19 in HCC remains elusive, a short outlook summarizes some ideas of using the H19 locus as a novel target for liver cancer therapy.