Expression of CHODL in hepatocellular carcinoma affects invasion and migration of liver cancer cells

Abstract Background Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6), a key protein involved in synthetizing dihydrotestosterone, is abundant in the liver. Previous studies have suggested a role for dihydrotestosterone in modulating progress of various malignancies, and HSD17B6 dysfunction was associated with lung cancer and prostate cancer. However, little is known about the detailed role of HSD17B6 in hepatocellular carcinoma (HCC). Methods Clinical implication and survival data related to HSD17B6 expression in patients with HCC were obtained through TCGA, ICGC, ONCOMINE, GEO and HPA databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The ChIP-seq data were obtained from Cistrome DB. Protein–Protein Interaction and gene functional enrichment analyses were performed in STRING database. The correlations between HSD17B6 and tumor immune infiltrates was investigated via TIMER and xCell. The proliferation, migration and invasion of liver cancer cells transfected with HSD17B6 were evaluated by the CCK8 assay, wound healing test and transwell assay respectively. Expression of HSD17B6, TGFB1 and PD-L1 were assessed by quantitative RT-PCR. Results HSD17B6 expression was lower in HCC compared to normal liver and correlated with tumor stage and grade. Lower expression of HSD17B6 was associated with worse OS, PFS, RFS and DSS in HCC patients. HNF4A bound to enhancer and promoter regions of HSD17B6 gene, activating its transcription, and DNA methylation of HSD17B6 promoter negatively controlled the expression. HSD17B6 and its interaction partners were involved in androgen metabolism and biosynthesis in liver. HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infiltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. Conclusions This study indicate that HSD17B6 could be a new biomarker for the prognosis of HCC and an important negative regulator of immune responses in HCC.

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ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells

Analytical Cellular Pathology ◽

10.1155/2019/1575031 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Hui Du ◽

Yun Le ◽

Fenyong Sun ◽

Kai Li ◽

Yanfeng Xu

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Cancer Cells ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Camp Response Element Binding ◽

Camp Response Element ◽

Liver Cancer Cells ◽

Binding Factor ◽

Element Binding Protein

Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) is overexpressed and has an oncogenic role in hepatocellular carcinoma (HCC). Interleukin enhancer binding factor 2 (ILF2) has become research hotspot in liver cancer recently. However, it is still unclear whether and how CREB and ILF2 interact with each other. And how this interaction exerts its role in occurrence and development of liver cancer is still unclear. Here, we found that ILF2 directly bound with CREB, and this binding was essential for the malignant phenotypes of liver cancer cells. Moreover, we found that ILF2 acted as one of the upstream proteins of CREB and promoted CREB only in the protein level, whereas ILF2 expression was not regulated by CREB. Mechanistically, ILF2 bound to the pKID domain of CREB and stimulated its phosphorylation at Ser133. Taken together, our study finds a novel interaction between CREB and ILF2 in liver cancer, and this interaction might play a role in the diagnosis and remedy of liver cancer.

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