Application of zkscan3 gene or protein inhibitor thereof in tumor therapy

An inhibitor and tumor technology, applied in the field of biomedicine, can solve problems affecting the development of B cells

Active Publication Date: 2019-07-05
PERSONGEN ANKE CELLULAR THERAPEUTICS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Whether Zkscan3 affects the developmen

Method used

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  • Application of zkscan3 gene or protein inhibitor thereof in tumor therapy
  • Application of zkscan3 gene or protein inhibitor thereof in tumor therapy
  • Application of zkscan3 gene or protein inhibitor thereof in tumor therapy

Examples

Experimental program
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Embodiment 1

[0071] Construction of zkscan3 knockout mice

[0072] ZKSCAN3 is highly expressed in a variety of human tumor tissues, but its role under normal physiological conditions remains largely unknown. Therefore, the inventors constructed a zkscan3 knockout mouse model. First construct the destination vector, insert the eGFP fragment and the polyA termination element before the start codon of the zkscan3 gene, insert the Neo gene wrapped by Frt sites on both sides downstream of the polyA, and install the same direction arrangement on the upstream and downstream of the entire insertion unit LoxP sites. Since eGFP utilizes the promoter of the zkscan3 gene to replace the expression of its reading frame, the expression level of eGFP represents the transcription level of zkscan3 ( figure 1 a-d).

[0073] Results: Zkscan3 knockout mice had no KRAB cDNA band, and wild mice had KRAB cDNA band ( figure 1 e). It shows that zkscan3 has been completely knocked out. The embryonic developmen...

Embodiment 2

[0075] In previous work, the inventors found that zkscan3 gene was highly expressed in human germinal centers, and guessed that it might be involved in the development of B cells. To test this hypothesis, the inventors systematically analyzed B cell development and plasma cell formation in a mouse model. Eight C57BL / 6 mice aged seven to eight weeks were selected, and zkscan3 knockout and wt mice contained similar numbers of bone marrow CD19+ B cells ( figure 2 a), and the number of bone marrow AA4+IgM-CD19+CD43+HSA+ primary B cells, AA4+IgM-CD19+CD43-HSA+ pre-B cells, and AA4+IgM+CD19+HSA+ naive B cells ( figure 2 b). Likewise, zkscan3 knockout and wt mice contained similar numbers of splenic CD19+ B cells ( figure 1 d), and CD19+ / IgM+ / IgD- / GL7+ germinal center B cells ( figure 2 e), CD19+ / B220+ / IgM+ / AA4- / CD23- / CD21 / 35+ marginal zone B cells ( figure 2 f), CD19+ / B220+ / IgM++ / AA4+ / CD23-T1 B cells, CD19+ / B220+ / IgM++ / AA4+ / CD23+T2 B cells, and CD19+ / B220+ / IgM+ / AA4- / CD23+ fo...

Embodiment 3

[0077] In order to further study the relationship between zkscan3 and plasma cell generation, the inventors constructed a colorectal cancer (MCA38cell) mouse model, and created a tumor microenvironment for the mice.

[0078] Results: In zkscan3 knockout mice, the number of plasma cells in the bone marrow increased dramatically compared with wild mice ( image 3 b*P image 3 c). BM CD19+ B cells, original B cells, pre-B cells, naive B cells, marginal zone B cells, T1B cells, T2B cells and T3B cells had no significant difference compared with wild mice ( image 3 a, d, e). It shows that the increase of plasma cells in zkscan3 knockout mice is more obvious when inoculated with MAC38 tumor cells.

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Abstract

The present invention provides an application of a zkscan3 gene or a protein modifier thereof in tumor therapy and particularly relates to a use of an inhibitor of the ZKSCAN3. The inhibitor of the ZKSCAN3 is used for preparation of a pharmaceutical composition promoting plasmocyte differentiation and proliferation, and/or treating tumors. The application provides a theoretical reference for a treatment strategy of selective knocking-out of the ZKSCAN3 in hematological tumors clinically, and has great significance for the clinical treatment of the hematological tumors targeting the ZKSCAN3.

Description

technical field [0001] The invention belongs to the field of biomedicine. Specifically, it relates to the application of zkscan3 gene or its protein regulator in tumor therapy. Background technique [0002] ZKSCAN3 is a zinc finger protein with KRAB and SCAN domains, and is a member of the zinc finger transcription factor family. ZKSCAN3 plays an important role in various types of human tumors. By up-regulating the expression of genes related to cell cycle, cell proliferation, migration, angiogenesis, and proteolysis, it promotes the progression of tumor progression, tumor cell invasion, migration, and growth and so on; while silencing its expression in tumor cells can significantly inhibit the malignant degree of tumor cells, inhibit the xenograft tumorigenicity of tumor cells, the growth and metastasis of tumor cells. Knocking out key molecules in tumor cells can inhibit tumor growth or enhance the anti-tumor effect of drugs, which is of great significance to the treatme...

Claims

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Application Information

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IPC IPC(8): C07K16/00C12N15/113C12N5/0781A61K45/00A61P35/00
CPCA61K45/00A61P35/00C07K16/00C12N5/0635C12N15/113
Inventor 杨林李自宣游凤涛
Owner PERSONGEN ANKE CELLULAR THERAPEUTICS CO LTD
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