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Tumor treatment target adaptive to hypoxia or hypoxia microenvironment and application thereof

A micro-environment and tumor technology, applied in anti-tumor drugs, medical preparations containing active ingredients, organic active ingredients, etc., to achieve the effect of solving poor therapeutic effects and good application prospects

Pending Publication Date: 2022-04-12
SHANGHAI TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, no studies have shown that FLAD1 and the FAD anabolic pathway play an important role in the adaptation of tumor cells to the hypoxic microenvironment, nor have any studies proposed that by targeting FLAD1 and the FAD anabolic pathway to selectively kill tumor cells that are deficient Oxygen status of tumor cells

Method used

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  • Tumor treatment target adaptive to hypoxia or hypoxia microenvironment and application thereof
  • Tumor treatment target adaptive to hypoxia or hypoxia microenvironment and application thereof
  • Tumor treatment target adaptive to hypoxia or hypoxia microenvironment and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] This example provides the application of FLAD1 in the targeted therapy of hypoxic or hypoxic tumors:

[0035] (1) Analysis of FLAD1 gene expression and copy number characteristics

[0036] Based on The Cancer Genome Atlas (TCGA) and Oncomine databases, the gene copy number and mRNA expression of FLAD1 were analyzed in hypoxic tumors (including lung cancer, breast cancer, prostate cancer, liver cancer, pancreatic cancer, melanoma, esophageal cancer, gastric cancer, thyroid cancer) expression in cancer, etc.), the results are as follows figure 1 As shown in A-D, the gene copy number and mRNA expression of FLAD1 were significantly upregulated in hypoxic tumors compared with non-hypoxic tumors.

[0037] (2) Knocking out FLAD1 can inhibit the proliferation of hypoxic tumor cells and reduce their tumorigenic ability in vivo

[0038] Construct sgRNA plasmid, use Benchling website to design sgRNA targeting FLAD1, such as figure 2 Shown in A, the sequence of gRNA of the pres...

Embodiment 2

[0060] This example provides the application of the FAD anabolic pathway in the targeted therapy of hypoxic or hypoxic tumors:

[0061] (1) The gene expression numbers of lung cancer samples in the TCGA database were analyzed by bioinformatics technology:

[0062] Based on the KEGG database to extract FAD metabolic pathways, such as Figure 4 As shown in A, by Figure 4 A shows that the main product of riboflavin metabolism is FAD, and the whole metabolism can be divided into two parts, one is the anabolism of FAD, and the other is the catabolism of FAD. Among them, the genes SLC52A1, SLC52A2, SLC52A3, RFK, and FLAD1 are involved in the anabolism of FAD , the genes ENPP1, ENPP3 and ACP5 are involved in the catabolism of FAD. By analyzing the gene expression data of lung adenocarcinoma patients on TCGA, comparing tumors with normal tissues, hypoxic tumors and non-hypoxic tumors, it was found that the FAD anabolic genes SLC52A1, SLC52A2, SLC52A3, RFK, and FLAD1 were in The ex...

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Abstract

The invention discloses a tumor treatment target adapting to a hypoxia or hypoxia microenvironment and application of the tumor treatment target. According to the invention, by constructing a tumor cell line with FLLA1 gene deletion, it is found that proliferation of tumor cells in a hypoxia state is significantly inhibited by FLLA1 deletion. According to the present invention, the FAD metabolism-related pathway in the KEGG database is extracted, and the gene expression of the sample in the TCGA database is analyzed, such that the riboflavin metabolism of the hypoxia tumor, especially the anabolism of the FAD, is significantly enhanced; by supplementing lumiflavin and a riboflavin degradation product into a cell culture medium of tumor cells, proliferation of the cells under hypoxia is obviously inhibited. The invention provides a brand new therapeutic target for clinical targeted therapy of hypoxia or hypoxia tumors, can solve the technical problems of poor therapeutic effect and poor prognosis caused by hypoxia adaptation of tumors at present, and has a good application prospect.

Description

technical field [0001] The invention relates to a class of therapeutic targets for tumors adapted to hypoxic or anoxic microenvironments and applications thereof, belonging to the technical fields of molecular biology and biomedicine. Background technique [0002] Tumor microenvironment (TME) is an important component of tumor tissue. Hypoxia is an important feature of the tumor microenvironment, present in approximately half of solid tumors 1 . Tumor hypoxia and clinically poorer prognosis observed in multiple cancer types 2,3 , and hypoxia is also associated with genome instability 4,5 , resistance to chemotherapy and radiotherapy 6 ,Immunosuppressive 7 , and immune escape 8 closely related. Existing studies suggest that tumor hypoxia is a major factor in resistance to anticancer therapy 9 . Targeted therapy of hypoxic tumor cells has always been an important scientific issue for clinical application. However, no corresponding treatment options have been develope...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/7105A61K31/525A61P35/00
Inventor 刘雪松赵翔宇
Owner SHANGHAI TECH UNIV
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