Wu Huajun, Zhong Zhiwei, Wang Anji, Yuan Chunhui, Ning Ke, Hu Huanhuan, Wang Chao, Yin Xiangbao
Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi Province China.
Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province China.
Cancer Cell Int. 2020 Jun 24;20:266. doi: 10.1186/s12935-020-01354-0. eCollection 2020.
The effect of lncRNA FTX on non-alcoholic fatty liver disease (NAFLD) conversion to hepatocellular carcinoma (HCC) is unclear.
In our study, C57BL/6 mice was fed with high fat diet for obtaining NAFLD mouse model, and diethylnitrosamine induced the formation of HCC tumor. The expression of iNOS and CD206 in tissues were examined using immunohistochemistry. In addition, qRT-PCR was implemented to detect the expression of FTX and mRNAs. The percentage of M1 and M2 Kupffer cells (KCs) were determined using flow cytometry. The pathological change in liver tissues was displayed by H&E staining. Besides, immunofluorescence assay was performed to ensure the primary KCs through labeling F4/80.
Here, we found that the expression of FTX and the ratio of M1/M2 KCs in liver tissues from NAFLD-transformed HCC (NAFLD-HCC) patients lower than in liver tissues from NAFLD patients. Subsequently, we revealed that the expression of FTX and M1/M2 KCs ratio were downregulated during NAFLD conversion to HCC. Importantly, increasing of FTX inhibited HCC tumor growth, improved liver damage and promoted M1 polarization of KCs during NAFLD conversion to HCC, while these effects of FTX were reversed by inactivating of KCs. Finally, in vitro experiments, our data indicated that FTX facilitated the M1 polarization of KCs.
In conclusion, our results demonstrated that upregulation of FTX suppressed NAFLD conversion to HCC though promoting M1 polarization of KCs. Our findings presented a new regulatory mechanism for NAFLD conversion to HCC, and provided a new biomarker for inhibiting this conversion.
长链非编码RNA FTX对非酒精性脂肪性肝病（NAFLD）转化为肝细胞癌（HCC）的影响尚不清楚。
在我们的研究中，给C57BL/6小鼠喂食高脂肪饮食以获得NAFLD小鼠模型，并用二乙基亚硝胺诱导HCC肿瘤形成。使用免疫组织化学检测组织中诱导型一氧化氮合酶（iNOS）和CD206的表达。此外，实施qRT-PCR检测FTX和mRNA的表达。使用流式细胞术测定M1和M2库普弗细胞（KCs）的百分比。通过苏木精-伊红（H&E）染色显示肝组织的病理变化。此外，进行免疫荧光测定以通过标记F4/80来确定原代KCs。
在这里，我们发现NAFLD转化的HCC（NAFLD-HCC）患者肝组织中FTX的表达以及M1/M2 KCs的比例低于NAFLD患者的肝组织。随后，我们发现FTX的表达和M1/M2 KCs比例在NAFLD转化为HCC的过程中下调。重要的是，在NAFLD转化为HCC的过程中，FTX的增加抑制了HCC肿瘤生长，改善了肝损伤并促进了KCs的M1极化，而FTX的这些作用被KCs的失活所逆转。最后，在体外实验中，我们的数据表明FTX促进了KCs的M1极化。
总之，我们的结果表明，FTX的上调通过促进KCs的M1极化抑制了NAFLD向HCC的转化。我们的发现提出了一种NAFLD转化为HCC的新调节机制，并为抑制这种转化提供了一种新的生物标志物。
