Clinical significance and function of RDH16 as a tumor‐suppressing gene in hepatocellular carcinoma

• Published in: Hepatology research Vol. 50; no. 1; pp. 110 - 120
• Main Authors: Zhu, Ying‐Hui, Li, Jian‐Biao, Wu, Rui‐Yan, Yu, Yan, Li, Xuan, Li, Zhi‐Ling, Zhang, Hai‐Liang, Feng, Gong‐Kan, Deng, Rong, Zhu, Xiao‐Feng
• Format: Journal Article
• Language: English
• Published: Netherlands Wiley Subscription Services, Inc 01.01.2020
• Subjects: Clinical significance; Ectopic expression; Gene expression; Hepatocellular carcinoma; Immunohistochemistry; Liver cancer; metastasis; Polymerase chain reaction; proliferation; Retinoic acid; Retinol dehydrogenase; retinol dehydrogenase 16; Sequence analysis; Thrombosis; Vitamin A; retinol dehydrogenase 16; retinoic acid; proliferation; metastasis; hepatocellular carcinoma
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/hepr.13432

Aim Our previous transcriptome sequencing analysis detected that retinol dehydrogenase 16 (RDH16) was dramatically downregulated in hepatocellular carcinoma (HCC). RDH16 belongs to the short‐chain dehydrogenases/reductases super family, and its role in HCC remains unknown. This study aimed to investigate the expression and function of RDH16 in HCC. Methods The mRNA and protein level of RDH16 in HCC samples were detected by quantitative real‐time polymerase chain reaction and immunohistochemistry analyses, respectively. The role of RDH16 in HCC was determined by in vitro and in vivo functional studies. Results Downregulation of RDH16 has been detected in approximately 90% of primary HCCs, which was significantly associated with high serum alpha‐fetoprotein level, tumor size, microsatellite formation, thrombus, and poor overall survival of HCC patients. Compared with non‐tumor tissues, higher density of methylation was identified in HCC samples. In addition, RDH16 increases the level of retinoic acid and blocks the de novo synthesis of fatty acid in HCC cells. Functional study shows that ectopic expression of RDH16 in HCC cells suppresses cell growth, clonogenicity, and cell motility. Conclusions RDH16 might be a prognostic biomarker and intervention point for new therapeutic strategies in HCC.