Hypoxia Induced ANKRD37 Promotes Angiogenesis and Reprograms Glucose Metabolism in Hepatocellular Carcinoma Following Liver Transplantation.

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Abstract

A liver graft before implantation experienced ischemic injury and facilitated a hypoxia microenvironment. However, the influence of hypoxia microenvironment to liver transplant recipients with hepatocellular carcinoma remains rarely discovered. Here we employed a hypoxia conditioning time-based cell model in order to screen fast responding genes when hypoxia occurred. Two liver cancer cell lines, HepG2 and SK-Hep1 were incubated at 1% O2 atmosphere for 2, 8 and 24 hours followed with next generation sequencing. Among thousands of disregulated mRNAs, microRNAs and lncRNAs, we distinguished that ANKRD37 was a direct downstream effector of hypoxia inducible factor 1 alpha (HIFa), and mediated critical hypoxia downstream biofunction. ANKRD37 elevated rapidly upon hypoxia occurred, and translocated into nucleus. Knockdown of ANKRD37 in HepG2 and SK-Hep1 decreased glucose intake and VEGFA secretion, also sensitized liver cancer cells to Sorafenib which is the only first line systemic therapy for hepatocellular carcinoma, while overexpression of ANKRD37 obtained opposite phenotype. In addition, higher expression of ANKRD37 was observed in liver cancer tissues compared with corresponding peri-tumor tissues. The co-expression analysis of ANKRD37 and HIF1a in liver cancer patients offered as a good prognosis predictor. Therefore, ANKRD37 might be a potential biomarker and therapeutical target for liver cancer patients underwent liver transplantation.

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