Cheng Wei, Cheng Ziwei, Yang Zongguo, Xing Dongwei, Zhang Minguang
Department of Radiology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People's Republic of China.
Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, People's Republic of China.
Onco Targets Ther. 2019 Aug 9;12:6285-6296. doi: 10.2147/OTT.S197077. eCollection 2019.
HIF1α mRNA expression in hepatocellular carcinoma (HCC) tissues and its relationship with the prognosis in HCC patients is still unclear. We performed this study to investigate the expression of HIF1α mRNA and its correlation with the prognosis in HCC patients.
GSE14520 and Oncomine database were used to analyse the differential expression of HIF1α mRNA among HCC tissues and corresponding peritumour tissues or normal liver tissues. The relationship between HIF1α mRNA expression and the clinicopathological features and survival in HCC patients was analysed using the GSE14520 dataset. CCK-8 assay, wound-healing assay, transwell invasion assay, tube formation assay, and subcutaneous xenograft tumour assays using nude mice were used to confirm the function of HIF1α.
Expression of HIF1α mRNA was significantly upregulated in HCC tissues (<0.05 in all cases); this was supported by the results of the Western blotting (=0.031) and IHC analyses. Our analysis of the clinicopathological features of HCC patients indicated that high HIF1α mRNA expression was strongly related with TNM stage III (=0.002) and BCLC stage C (=0.038). Survival analysis demonstrated that HCC patients with high HIF1α mRNA expression had a short overall survival (OS) (=0.048), but showed no significant difference in recurrence-free survival (RFS) (=0.066) compared to patients with low HIF1α mRNA expression. We further demonstrated that HIF1α promoted the proliferation, migration, invasion, and angiogenic ability of HCC cells, by using the tably transformed SK-Hep1 and Hep-3B cell lines showing HIF1α overexpression. Finally, xenograft tumour models of nude mice showed that RNA interference-mediated HIF1α silencing suppressed tumour growth and angiogenesis in HCC.
Our study suggests that the upregulation of HIF1α mRNA, which is found in HCC tissues and associated with poor prognosis in HCC patients, contributed to the proliferation, migration, invasion, and angiogenic ability of HCC cells.
肝细胞癌（HCC）组织中HIF1α mRNA的表达及其与HCC患者预后的关系仍不清楚。我们进行了这项研究以调查HIF1α mRNA的表达及其与HCC患者预后的相关性。
使用GSE14520和Oncomine数据库分析HCC组织与相应癌旁组织或正常肝组织中HIF1α mRNA的差异表达。使用GSE14520数据集分析HIF1α mRNA表达与HCC患者临床病理特征及生存的关系。采用CCK-8法、伤口愈合试验、Transwell侵袭试验、管腔形成试验以及使用裸鼠的皮下异种移植肿瘤试验来证实HIF1α的功能。
HIF1α mRNA在HCC组织中的表达显著上调（所有病例中P<0.05）；蛋白质免疫印迹（P=0.031）和免疫组化分析结果支持了这一点。我们对HCC患者临床病理特征的分析表明，HIF1α mRNA高表达与TNM III期（P=0.002）和BCLC C期（P=0.038）密切相关。生存分析表明，HIF1α mRNA高表达的HCC患者总生存期（OS）较短（P=0.048），但与HIF1α mRNA低表达的患者相比，无复发生存期（RFS）无显著差异（P=0.066）。我们进一步证明，通过使用稳定转染的显示HIF1α过表达的SK-Hep1和Hep-3B细胞系，HIF1α促进了HCC细胞的增殖、迁移、侵袭和血管生成能力。最后，裸鼠异种移植肿瘤模型表明，RNA干扰介导的HIF1α沉默抑制了HCC中的肿瘤生长和血管生成。
我们的研究表明，HCC组织中发现的HIF1α mRNA上调与HCC患者预后不良相关，其促进了HCC细胞的增殖、迁移、侵袭和血管生成能力。
