Clinical significance and function of RDH16 as a tumor-suppressing gene in hepatocellular carcinoma
Clinical significance and function of RDH16 as a tumor-suppressing gene in hepatocellular carcinoma
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RDH16 作为抑癌基因在肝细胞癌中的临床意义和功能
DOI：
10.1111/hepr.13432
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发表时间：
2019-12-08
影响因子：
4.2
通讯作者：
Zhu, Xiao-Feng
中科院分区：
文献类型：
--
作者：
Zhu, Ying-Hui;Li, Jian-Biao;Zhu, Xiao-Feng
目的通过转录组测序分析发现肝细胞癌（HCC）中视黄醇脱氢酶16（RDH 16）表达显著下调。RDH 16属于短链淀粉酶/还原酶超家族，其在HCC中的作用尚不清楚。本研究旨在探讨RDH 16在肝癌中的表达及功能。方法采用实时荧光定量聚合酶链反应（RT-PCR）和免疫组化方法分别检测肝癌组织中RDH 16的mRNA和蛋白水平。通过体外和体内功能研究确定RDH 16在HCC中的作用。结果RDH 16在90%的原发性肝癌中表达下调，与肝癌患者血清甲胎蛋白水平升高、肿瘤大小、微卫星形成、血栓形成及总生存率降低显著相关。与非肿瘤组织相比，在HCC样品中鉴定到更高的甲基化密度。此外，RDH 16增加HCC细胞中视黄酸的水平并阻断脂肪酸的从头合成。功能研究表明，RDH 16在HCC细胞中的异位表达抑制细胞生长、克隆形成和细胞运动。结论RDH 16可能是HCC预后的生物标志物和新的治疗策略的干预点。
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.