Application of cebpα as the target site of ranbp2 in the preparation of glycosylation drugs for the treatment of liver cancer

A RANBP2, 1. RANBP2 technology, applied in the field of diagnosis and treatment of glycosylation-related drugs in hepatocellular carcinoma, can solve the problem of decreased expression level

Active Publication Date: 2022-04-12
THE THIRD XIANGYA HOSPITAL OF CENT SOUTH UNIV
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  • Claims
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Problems solved by technology

Previous studies have found that the level of O-glycosylation modification in HCC is significantly higher than that in normal tissues and adjacent tissues, while the expression level of OGA protein is generally decreased.

Method used

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  • Application of cebpα as the target site of ranbp2 in the preparation of glycosylation drugs for the treatment of liver cancer
  • Application of cebpα as the target site of ranbp2 in the preparation of glycosylation drugs for the treatment of liver cancer
  • Application of cebpα as the target site of ranbp2 in the preparation of glycosylation drugs for the treatment of liver cancer

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Embodiment Construction

[0029] The present invention will be further explained and illustrated below in conjunction with the accompanying drawings and experimental data.

[0030] , materials and methods

[0031] Cell culture and transfection, qRT-PCR analysis, Western blot analysis, immunohistochemical assay, MTT assay, flow cytometry, immunoprecipitation, chromatin immunoprecipitation, immunofluorescence, dual luciferase assay, flow cytometry For the determination of Lipid-ROS, the above methods are all existing methods and will not be repeated here.

[0032] ,result

[0033] 2.1 RANBP2 is highly expressed in liver cancer tissues, which can cause the decrease of OGA expression

[0034] We first measured the expression of RANBP2 in 50 cases of clinical cancer tissues and adjacent tissues by immunohistochemistry and Western blot, and found that the immunohistochemical score of RANBP2 in liver cancer tissues was significantly higher than that in corresponding adjacent tissues ( figure 1 A, 1B). Cel...

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Abstract

The invention discloses the application of CEBPα as a detection reagent of RANBP2 target site in the preparation of glycosylation-related drugs for treating liver cancer. The study of the present invention shows that the high expression of RANBP2 in liver cancer cells is positively correlated with the malignant phenotype of liver cancer. RANBP2 down-regulates the expression of OGA, increases O-glycosylation modification, and then increases the proliferation and invasion ability of liver cancer cells. As a key transcription factor CEBPα that positively regulates OGA, RANBP2 can induce the SUMOylation of CEBPα, and experiments have confirmed that the K196 site of CEBPα is the key SUMO target site of RANBP2, and SUMOylation of this site can promote the degradation of CEBPα protein. Protecting the K196 site of CEBPα from SUMOylation or increasing the expression of CEBPα itself can slow down the OGA-mediated O-glycosylation pathway.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of transcription factor CEBPα as a target of RANBP2 in the diagnosis and treatment of glycosylation-related drugs in hepatocellular carcinoma. Background technique [0002] Hepatocellular carcinoma (HCC) is a malignant tumor that seriously plagues and threatens the health of modern people, accounting for 18.8% of the total number of malignant tumor deaths. Although surgical resection, liver transplantation, postoperative radiotherapy and chemotherapy, and molecular targeted therapy have made great progress in the treatment of liver cancer, the overall survival rate of liver cancer patients has not improved significantly compared to before. Hepatocellular carcinoma has the characteristics of high recurrence rate, high mortality rate, and poor prognosis. The reason is that the early diagnosis and examination methods of liver cells are not standardized...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P35/00
CPCA61K45/00A61P35/00
Inventor 曹科刘晓明陈兴宇
Owner THE THIRD XIANGYA HOSPITAL OF CENT SOUTH UNIV
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