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Application of C/EBP beta gene or protein

A β gene and application technology, applied in medical preparations containing active ingredients, microbial determination/inspection, biochemical equipment and methods, etc., can solve the problem of lack of anti-tumor drugs, poor prognosis of drug resistance and lack of tumor drug resistance And other issues

Active Publication Date: 2019-09-24
TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to overcome the lack of markers that can be used to evaluate tumor drug resistance and prognosis in the prior art for the phenomenon of drug resistance and poor prognosis in the process of tumor treatment, and further lack of antitumor drugs defect, providing a use of C / EBPβ gene or protein

Method used

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  • Application of C/EBP beta gene or protein
  • Application of C/EBP beta gene or protein
  • Application of C/EBP beta gene or protein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Overexpression of C / EBPβ can reduce the sensitivity of cells to cisplatin, and inhibiting the expression of C / EBPβ can increase the sensitivity of cells to cisplatin

[0034] 1. Methylation analysis

[0035] Serous ovarian cancer is the most common and most malignant ovarian cancer. The tissue of origin of serous ovarian cancer is the fallopian tube epithelium. The specimens of normal fallopian tube, high-grade serous ovarian cancer (HG-SOC) and low-grade serous ovarian cancer (LG-SOC) were purified by using the epithelial marker EPCAM and magnetic bead sorting method ( figure 1 ), six major histone methylation sites (H3K4, H3K9, H3K27, H3K36, H3K79 and H4K20) were analyzed. Chromatin immunoprecipitation combined with high-throughput sequencing (ChIP-Sequencing) was used to analyze the degree of histone methylation in each group of samples.

[0036] The results showed that HG-SOC was mainly increased by H3K4me3, H3K9me3 and H3K79me3, while LG-SOC had little...

Embodiment 2

[0042] Example 2 The promoting effect of C / EBPβ on platinum resistance is mediated by DOT1L, and C / EBPβ-DOT1L can be used as a new target in molecular targeted therapy.

[0043] 1. C / EBPβ can promote H3K79 methylation

[0044] Using H3K79 methylation antibody for ChIP-Sequencing analysis, the results showed that silencing C / EBPβ reduced the overall H3K79 methylation level of C13* cells ( Figure 8 A). At the same time, the present invention uses the C / EBPβ antibody to perform ChIP-Sequencing to identify the C / EBPβ target gene. C / EBPβ target genes were significantly associated with genes with reduced H3K79 methylation levels after C / EBPβ silencing ( Figure 8 B, 8C). Since the increased methylation of H3K79 promotes gene expression (Nat Rev Mol Cell Biol.2005; 6(11):838-49), the present invention uses RNA-Sequencing to analyze the genes regulated by C / EBPβ ( Figure 8 D-8F). Finally, the changes in H3K79 methylation and gene expression levels caused by silencing C / EBPβ wer...

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Abstract

The invention discloses application of a C / EBP beta gene or protein, and particularly discloses the application of the C / EBP beta gene or protein to preparation of a biomarker for assessing the risk of drug resistance in cancer and / or prognosis of patients, wherein the cancer is an ovarian cancer or a breast cancer. The drug resistance mechanism of cancer cells is studied from a new perspective, it is found that C / EBP beta mediates chemoresistance by reprogramming the expression of numerous drug resistance genes, and it is revealed that DOT1L is histone methyltransferase which mediates C / EBP beta regulation. The application of the C / EBP beta gene or protein provides a basis for assessing the risk of drug resistance in the ovarian cancer or the breast cancer and the prognosis of the patients as well as screening for drugs for the ovarian cancer or the breast cancer. A novel and more precise target is provided for molecular targeted therapy of cancers, especially the ovarian cancer and the breast cancer, and a foundation is laid for screening drugs suitable for cisplatin combined chemotherapy (novel enzyme inhibitors).

Description

technical field [0001] The invention belongs to the field of biomedicine, specifically relates to the field of ovarian cancer drug resistance, in particular to the use of a C / EBPβ gene or protein. Background technique [0002] Chemotherapy is one of the most important methods in clinical tumor treatment at present, and it can usually achieve better therapeutic effect within a certain period of time. However, during the course of treatment, tumor cells gradually develop drug resistance, which greatly restricts the effect of chemotherapy. Ovarian cancer is the gynecological tumor with the highest fatality rate. Its onset process is hidden, and 70% of the patients are already in the advanced stage when they are first diagnosed. Cytoreductive surgery and postoperative platinum-based chemotherapy are currently the main treatment options for ovarian cancer. However, since most patients eventually develop chemotherapy resistance, the 5-year survival rate for patients with advance...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574A61K45/00A61P35/00
CPCC12Q1/6886G01N33/57415G01N33/57449A61K45/00A61P35/00C12Q2600/154C12Q2600/158C12Q2600/118C12Q2600/106
Inventor 马丁高庆蕾刘眈张小雪李梦晨黄晓园
Owner TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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