3篇
您的检索式：作者名="Daimin Xiang"
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| 1 | m6A RNA methylation-mediated HNF3γreduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance显示文摘Hepatocyte nuclear factor 3γ(HNF3γ)is a hepatocyte nuclear factor,but its role and clinical significance in hepatocellular carcinoma(HCC)remain unclear.Herein,we report that HNF3γexpression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival.Moreover,our data suggested that the HNF3γreduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γmRNA.HNF3γexpression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells.Interestingly,HNF3γdelivery promoted differentiation of not only HCC cells but also liver CSCs,which led to suppression of HCC growth.Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules,which could synergistically facilitate HCC cell differentiation.More importantly,enforced HNF3γexpression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression,which are major membrane transporters for sorafenib uptake.Clinical investigation showed that patient-derived HCC xenografts with high HNF3γexpression exhibited a sorafenib response and patients with high HCC HNF3γlevels benefited from sorafenib therapy.Together,these results suggest that HNF3γplays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients. | Tengfei Zhou Shichao Li Daimin Xiang Junyu Liu Wen Sun Xiuliang Cui Beifang Ning Xiao Li Zhuo Cheng Weiqi Jiang Cheng Zhang Xijun Liang Liang Li Xin Cheng Liu Hui Hongyang Wang Jin Ding | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 4 |
| 2 | Conversion of hepatoma cells to hepatocyte-like cells by defined hepatocyte nuclear factors显示文摘Normal cells become cancer cells after a malignant transformation,but whether cancer cells can be reversed to normal status remains elusive.Here,we report that the combination of hepatocyte nuclear factor IA (HNFIA),HNF4A and forkhead box protein A3 (FOXA3)synergistically reprograms hepatocellular carcinoma (HCC)cells to hepatocyte-like cells (reprogrammed hepatocytes, rHeps).Our results show that rHeps lose the malignant phenotypes of cancer cells and retrieve hepatocyte-specific characteristics including hepatocyte-like morphology;global expression pattern of genes and specific biomarkers of hepatocytes;and the unique hepatic functions of albumin (ALB)secretion,glycogen synthesis,low-density lipoprotein (LDL)uptake,urea production, cytochrome P450 enzymes induction and drug metabolism.Intratumoral injection of these three factors efficiently shrank patientderived tumor xenografts and reprogrammed HCC cells in vivo.Most importantly,transplantation of rHeps in the liver of fumarylacetoacetate hydrolase-deficient (Fah^-/-)mice led to the reconstruction of hepatic lobules and the restoration of hepatic function.Mechanistically,exogenous expression of HNF1A,HNF4A and FOXA3 in HCC cells initiated the endogenous expression of numerous hepatocyte nuclear factors,which promoted the conversion of HCC cells to hepatocyte-like cells.Collectively,our results indicate the successful conversion of hepatoma cells to hepatocyte-like cells,not only extending our current knowledge of cell reprogramming but also providing a route towards a novel therapeutic strategy for cancer. | Zhuo Cheng Zhiying He Yongchao Cai Cheng Zhang Gongbo Fu Hengyu Li Wen Sun Changcheng Liu Xiuliang Cui Beifang Ning Daimin Xiang Tengfei Zhou Xiaofeng Li Weifen Xie Hongyang Wang Jin Ding | 2019 | Cell Research2019，29，2： | 3 |
| 3 | m6A RNA methylation-mediated HNF3γ reduction rendershepatocellular carcinoma dedifferentiation and sorafenibresistance显示文摘Hepatocyte nuclear factor 3γ(HNF3γ)is a hepatocyte nuclear factor,but its role and clinical significance in hepatocellular carcinoma(HCC)remain unclear.Herein,we report that HNF3γexpression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival.Moreover,our data suggested that the HNF3γreduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γmRNA.HNF3γexpression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells.Interestingly,HNF3γdelivery promoted differentiation of not only HCC cells but also liver CSCs,which led to suppression of HCC growth.Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules,which could synergistically facilitate HCC cell differentiation.More importantly,enforced HNF3γexpression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression,which are major membrane transporters for sorafenib uptake.Clinical investigation showed that patient-derived HCC xenografts with high HNF3γexpression exhibited a sorafenib response and patients with high HCC HNF3γlevels benefited from sorafenib therapy.Together,these results suggest that HNF3γplays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients. | Tengfei Zhou Shichao Li Daimin Xiang Junyu Liu Wen Sun Xiuliang Cui Beifang Ning Xiao Li Zhuo Cheng Weiqi Jiang Cheng Zhang Xijun Liang Liang Li Xin Cheng Liu Hui Hongyang Wang Jin Ding | 2021 | Signal Transduction and Targeted Therapy2021，6，1： | 0 |
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