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Application of YOD1 gene in preparation of leukemia induced differentiation treatment drug

A technology for inducing differentiation and treating drugs, which is applied in the field of medicine and biology, can solve the problems of YOD1 gene and leukemia cell differentiation that have not been reported in the literature, and achieve the effect of improving drug resistance and related prognosis and improving curative effect

Active Publication Date: 2020-07-10
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These studies all suggest that YOD1 protein regulates the ubiquitination level of related proteins to participate in important life activities of cells, but the relationship between YOD1 gene and leukemia cell differentiation has not been reported in the literature, and further research is needed

Method used

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  • Application of YOD1 gene in preparation of leukemia induced differentiation treatment drug
  • Application of YOD1 gene in preparation of leukemia induced differentiation treatment drug
  • Application of YOD1 gene in preparation of leukemia induced differentiation treatment drug

Examples

Experimental program
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Effect test

Embodiment 1

[0026] Seven YOD1 siRNAs targeting different sequences (SEQ ID NO:3-SEQ ID NO:9) and the negative control NC were introduced into NB4 cells by lipofection (Dr. Lingtao Wu, University of Southern California, USA). After 72 hours, the cells were harvested, and the cells were lysed with the cell lysate to extract proteins, and then western blot was performed with YOD1 antibody (purchased from Proteintech). As a result, it was found that all the above YOD1 siRNAs (SEQ ID NO:3-SEQ ID NO:9) could effectively inhibit the protein expression of YOD1. See results figure 1 .

Embodiment 2

[0028] Two YOD1 siRNAs targeting different sequences with different silencing efficiencies (SEQ ID NO:3,SEQ ID NO:4) and the negative control NC were introduced into leukemia NB4, U937 and HL60 cells by lipofection (purchased from the Cell Bank of the Chinese Academy of Sciences). After treatment D1, D3 and D5, counts were performed using a hemocytometer. The results showed that YOD1 siRNA (SEQ ID NO:3, SEQ ID NO:4) could significantly inhibit the proliferation of leukemia NB4, U937 and HL60 cells. See results figure 2 .

Embodiment 3

[0030] YOD1 siRNA (SEQ ID NO:3, SEQ ID NO:4) targeting different sequences with different silencing efficiencies and the negative control NC were introduced into NB4 cells by lipofection. The cells were collected after treatment on D3 and D5, and the expression of the differentiation-specific antigen CD11b on the cell surface was detected. Cells were rinsed with ice PBS for 3 times and then incubated with 1% BSA and CD11b-PE-labeled monoclonal antibody in the dark for 60 min. After washing with PBS, the cells were detected by flow cytometry and analyzed by CellQuest Pro software. As a result, it was found that YOD1 siRNA (SEQ ID NO:3, SEQ ID NO:4) can significantly promote the expression of the specific antigen CD11b on the surface of leukemia cells. See results image 3 .

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Abstract

The invention provides application of a YOD1 gene in preparation of a leukemia induced differentiation treatment drug. The YOD1 gene comprises polypeptide targeting the YOD1 gene, a small molecule inhibitor targeting YOD1 protein and interference siRNAs targeting the YOD1 gene. By utilizing a siRNA interference technology, differentiation of leukemia NB4 cells can be induced by reducing expressionof YOD1. Differentiation of human leukemia cells can be effectively induced by reducing YOD1; a new direction is provided for development of the current leukemia treatment drug, so that the awkward situations of few available drugs, single mechanism and the like of the clinical leukemia induced differentiation drug are solved to a certain degree, a new research field is opened up for leukemia treatment, and the possibility is provided for preparation of the new induced differentiation leukemia drug, improvement of the curative effect of leukemia patients and improvement of drug resistance andrelated prognosis conditions. The invention provides a new treatment target for induced differentiation treatment of leukemia.

Description

technical field [0001] The invention belongs to the technical field of medicine and biology, and specifically relates to the application of a YOD1 gene in the preparation of medicines for inducing differentiation of leukemia. Background technique [0002] Leukemia is a class of malignant clonal diseases of hematopoietic stem cells characterized by clinical and biological heterogeneity and severe differentiation disorders. After decades of research, researchers have made some progress in understanding the pathology and genomics of leukemia, and aiming at the important characteristics of leukemia differentiation disorder, scientists have proposed induction differentiation therapy for the treatment of leukemia. Currently, differentiation therapy using all-trans retinoic acid has achieved great success in the APL subtype of leukemia. However, the application of clinical induction differentiation therapy is currently limited to APL subtypes, and there are very few drugs to choos...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K38/16A61K31/7088A61P35/02
CPCA61K31/7088A61K38/16A61K45/00A61P35/02
Inventor 应美丹何俏军杨波邵雪晶陈颖倩曹戟朱虹
Owner ZHEJIANG UNIV
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