A TNFR2-hnRNPK axis promotes primary liver cancer development via activation of YAP signaling in hepatic progenitor cells

2021 ◽  
pp. canres.3175.2020
Author(s):  
Yan Meng ◽  
Qiudong Zhao ◽  
Liwei An ◽  
Shi Jiao ◽  
Rong Li ◽  
...  
Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 506 ◽  
Author(s):  
Edie-Rosmin Wu ◽  
Ying-Erh Chou ◽  
Yu-Fan Liu ◽  
Kuan-Chun Hsueh ◽  
Hsiang-Lin Lee ◽  
...  

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, whose diversified occurrence worldwide indicates a connection between genetic variations among individuals and the predisposition to such neoplasms. Mounting evidence has demonstrated that long non-coding RNA (lncRNA) H19 can have both promotive and inhibitory effects on cancer development, revealing a dual role in tumorigenesis. In this study, the link of H19 gene polymorphisms to hepatocarcinogenesis was assessed between 359 HCC patients and 1190 cancer-free subjects. We found that heterozygotes for the minor allele of H19 rs2839698 (T) and rs3741219 (G) were more inclined to develop HCC (OR, 1.291; 95% CI, 1.003–1.661; p = 0.047, and OR, 1.361; 95% CI, 1.054–1.758; p = 0.018, respectively), whereas homozygotes for the polymorphic allele of rs2107425 (TT) were correlated with a decreased risk of HCC (OR, 0.606; 95% CI, 0.410–0.895; p = 0.012). Moreover, patients who bear at least one variant allele (heterozygote or homozygote) of rs3024270 were less prone to develop late-stage tumors (for stage III/IV; OR, 0.566; 95% CI, 0.342–0.937; p = 0.027). In addition, carriers of a particular haplotype of three H19 SNPs tested were more susceptible to HCC. In conclusion, our results indicate an association between H19 gene polymorphisms and the incidence and progression of liver cancer.


2019 ◽  
Vol 70 (1) ◽  
pp. e376
Author(s):  
Nofar Rosenberg ◽  
Matthias Van Haele ◽  
tania roskams ◽  
Mathias Heikenwälder ◽  
Klaus Kaestner ◽  
...  

2018 ◽  
Vol 68 ◽  
pp. S669
Author(s):  
N. Rosenberg ◽  
N. Barashi ◽  
H. Giladi ◽  
D. Goldenberg ◽  
M. Shoshkes-Carmel ◽  
...  

Oncogene ◽  
2019 ◽  
Vol 39 (8) ◽  
pp. 1807-1820 ◽  
Author(s):  
Ke-shuai Dong ◽  
Yan Chen ◽  
Guang Yang ◽  
Zhi-bin Liao ◽  
Hong-wei Zhang ◽  
...  

AbstractIncreasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-β1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-β1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-β1 than in those with high HBx or high TGF-β1 and the double-low-expression group. HBx and TGF-β1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-β1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial–mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-β1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-β1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-β1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.


2019 ◽  
Author(s):  
Kyungsik Ha ◽  
Masashi Fujita ◽  
Rosa Karlić ◽  
Sungmin Yang ◽  
Yujin Hoshida ◽  
...  

AbstractBackgroundPrimary liver tissue cancers display consistent increase in global disease burden and mortality. Identification of cell-of-origins for primary liver cancers would be a necessity to expand options for designing relevant therapeutics and preventive medicine for these cancer types. Previous reports on cell-of-origin for primary liver cancers was mainly from animal studies, and integrative research utilizing human specimen data was poorly established.MethodsWe analyzed a whole-genome sequencing data set for a total of 363 tumor and progenitor tissues along with 423 normal tissue epigenomic marks to predict the cell-of-origin for primary liver cancer subtypes.ResultsDespite the mixed histological features, the predicted cell-of-origin for mixed hepatocellular carcinoma / intrahepatic cholangiocarcinoma were uniformly predicted as a hepatocytic origin. Individual sample-level prediction revealed differential level of cell-of-origin heterogeneity depending on the primary liver cancer types, with more heterogeneity observed in intrahepatic cholangiocarcinomas. Additional analyses on the whole genome sequencing data of hepatic progenitor cells suggest these progenitor cells might not a direct cell-of-origin for liver cancers.ConclusionsThese results provide novel insights on the heterogeneous nature and potential contributors of cell-of-origin predictions for primary liver cancers.


2010 ◽  
Vol 34 (8) ◽  
pp. S41-S41
Author(s):  
Yang Bi ◽  
Yun He ◽  
Tingyu Li ◽  
Tao Feng ◽  
Tongchuan He

2001 ◽  
Vol 120 (5) ◽  
pp. A542-A543
Author(s):  
T HIROSE ◽  
K YASUCHIKA ◽  
T FUJIKAWA ◽  
H FUJII ◽  
S OE ◽  
...  

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