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Aldehyde dehydrogenase 18A1 gene and application of encoding product thereof to MYCN amplification neuroblastoma

A neuroblastoma, acetaldehyde dehydrogenase technology, applied in the field of biomedicine

Active Publication Date: 2019-12-06
THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the relationship between ALDH18A1 and MYCN gene amplification in NB patients has not been reported

Method used

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  • Aldehyde dehydrogenase 18A1 gene and application of encoding product thereof to MYCN amplification neuroblastoma
  • Aldehyde dehydrogenase 18A1 gene and application of encoding product thereof to MYCN amplification neuroblastoma
  • Aldehyde dehydrogenase 18A1 gene and application of encoding product thereof to MYCN amplification neuroblastoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1. Relationship between ALDH18A1 and MYCN gene amplification in NB patients

[0031] To study the relationship between ALDH18A1 and MYCN gene amplification in NB patients, GSE16476, GSE13136, GSE12460, E-MEXP-669 and GSE45547 (containing 88, 30, 47, 18 and 649 NB patients, respectively), and E- ALDH18A1 mRNA expression level and MYCN gene amplification in MTAB-161, E-MTAB-179 and E-MTAB-1781 large sample databases, the results are as follows figure 1 , A~D, figure 2 and image 3 , shown in A~C. The results showed that there was a positive correlation between the expression level of ALDH18A1mRNA and MYCN gene amplification and MYCN overexpression. At the same time, using 17 NB cell lines in the Encyclopedia of Cancer Cell Lines for analysis, the same results were also obtained ( image 3 , D). Further, Gene Set Enrichment Analysis (GSEA) on the GSE16476 database suggested that in NB patients with high expression of ALDH18A1, MYCN target gene sets (NMYC_01, ...

Embodiment 2

[0033] Example 2, the relationship between the expression of ALDH18A1 and the clinicopathological parameters of NB patients

[0034] To further study the relationship between ALDH18A1 and NB clinicopathological parameters. Using the above-mentioned 49 NB patients and 5 normal tissues to compare, it was found that the expression level of ALDH18A1 was significantly increased in NB ( Figure 5 , A). Analysis of the GSE16476 database indicated that the expression of ALDH18A1mRNA was higher in patients with older onset age (greater than 12 months), higher INSS tumor grade and tumor metastasis ( Figure 5 , B-E), the analysis of E-MTAB-161, E-MTAB-179 and E-MTAB-1781 databases also obtained similar results ( Figure 6 and Table 1). At the same time, the analysis of the 49 NB clinical samples above showed that the ALDH18A1 protein level was also closely related to risk factors such as INSS tumor grade and MYCN copy number ( Figure 4 , C and D, Figure 5 , F and G).

[0035] Ta...

Embodiment 3

[0052] Example 3, ALDH18A1 promotes the proliferation, self-renewal and tumor initiation ability of NB cells

[0053] The method of down-regulating the expression of ALDH18A1: connect the shRNA sequence in Table 7 to the BamHI and EcoRI restriction sites of the pLVshRNA-EGFP vector, and transfer it into 293T cells together with the psPAX2 and PMD2.G packaging plasmids, and collect the lentivirus after 48 hours Clear, concentrate, and purify. This lentivirus was used to infect neuroblastoma cell lines IMR32 and SK-N-BE(2). After amplification, GFP-positive cells were screened by flow cytometry, and a single clone was further selected to down-regulate the expression of ALDH18A1.

[0054] Table 7, ShRNA sequence of ALDH18A1

[0055]

[0056] Up-regulation of ALDH18A1 expression method: connect the ALDH18A1 ORF sequence (GenBank: NG_012258.1; SEQ ID NO.7) to the EcoRI and BamHI restriction sites of the pLV-EGFP-C vector, and transfer it into 293T together with the psPAX2 and P...

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Abstract

The invention relates to an aldehyde dehydrogenase 18A1 gene and application of an encoding product thereof to MYCN amplification neuroblastoma. The aldehyde dehydrogenase 18A1 gene can serve as a target point for therapy and drug screening of the MYCN amplification neuroblastoma, and a new idea is provided for therapy and drug screening of the MYCN amplification neuroblastoma; and meanwhile, thealdehyde dehydrogenase 18A1 gene can further serve as a diagnostic marker for the MYCN amplification neuroblastoma, can be used for early diagnosis and prognostic monitoring of the MYCN amplificationneuroblastoma, and is of great clinical significance for therapy and diagnosis of the MYCN amplification neuroblastoma.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to the application of acetaldehyde dehydrogenase 18A1 gene and its coded product in MYCN amplified neuroblastoma. Background technique [0002] Neuroblastoma (NB) is the most common peripheral nervous system tumor in children. MYCN amplification is seen in about 20% of NB patients and is the most important adverse prognostic factor for NB patients. Exploring treatment options and drugs targeting MYCN has important clinical significance. However, due to the structural specificity of the protein encoded by MYCN, N-myc, which makes direct attachment of small-molecule drugs difficult, the molecule is notoriously considered undruggable. Therefore, starting from the upstream and downstream of MYCN to find new NB intervention targets is an important direction of exploration. [0003] Aldehyde dehydrogenase 18A1 (aldehyde dehydrogenase 18A1, ALDH18A1) gene encodes pyrroline-5-carboxylate synthas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574G01N33/573A61K45/00A61K31/7088A61P35/00
CPCC12Q1/6886G01N33/57407G01N33/573A61K45/00A61K31/7088A61P35/00C12Q2600/118C12Q2600/106G01N2333/90203
Inventor 余时沧郭玉峰段江洁
Owner THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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