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Application to promotion of cervical squamous cell carcinoma metastasis based on DDX19A

A technology for squamous cell carcinoma and cervix, which is applied in the field of promoting the metastasis of cervical squamous cell carcinoma based on DDX19A, and can solve the problems of DEAD-box protein expression and unclear function

Active Publication Date: 2021-05-18
THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the expression and function of DEAD-box protein in cervical squamous cell carcinoma is still unclear

Method used

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  • Application to promotion of cervical squamous cell carcinoma metastasis based on DDX19A
  • Application to promotion of cervical squamous cell carcinoma metastasis based on DDX19A
  • Application to promotion of cervical squamous cell carcinoma metastasis based on DDX19A

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Correlation between DDX19A and cervical squamous cell carcinoma

[0046] 1. Bioinformatics and data analysis

[0047] Normal cervical tissue and cervical squamous cell carcinoma (SCC) tissue were examined according to The Cancer Genome Atlas (TCGA; https: / / gdc.cancer.gov / ) and the Gene Expression Bank (GEO) dataset (GSE7803). Expression of DDX19A mRNA (see https: / / www.ncbi.nlm.nih.gov / geo). Gene expression is expressed as the mean of multiple probes per gene after log2 transformation. Comparisons (normal cervical tissue versus cervical squamous cell carcinoma tissue) were analyzed by the Mann-Whitney U test, and p<0.05 was considered statistically significant.

[0048] 2. Immunohistochemical staining

[0049] Cervical squamous cell carcinoma and adjacent normal tissues (76 pairs) and 10 unpaired cervical squamous cell carcinoma tissues were used to prepare TMA. DDX19A antibody or NOX1 antibody were used to detect the expression of DDX19A and NOX1 proteins,...

Embodiment 2

[0064] Example 2 DDX19A promotes the metastasis of cervical squamous cell carcinoma cells in vivo and in vitro

[0065] Using bioinformatics analysis and confirmatory experiments in clinical specimens, we found that the expression of DDX19A was positively correlated with tumor metastasis. In addition, the occurrence of metastasis is an important reason for the poor prognosis of patients with cervical squamous cell carcinoma. To verify the function of DDX19A in cervical squamous cell carcinoma metastasis, we performed functional studies in vitro and in vivo.

[0066] 1. Protein expression of DDX19A and NOX1 at the cellular level by protein separation and Western blot analysis.

[0067] 2. Using DDX19A-specific short hairpin RNA (shRNA, 5'-GTACTCGGTGAAGTCGTTT-3' and 5'-CTGTCAAGTCGATGACCAA-3'), DDX19A-specific siRNA (5'-CTGTCAAGTCGATGACCAA-3' and 5'-GGCAGTATATCTTTGTTAA-3' ), NOX1-specific siRNA (5'-GATCGTGACTCCCACTGTA-3' and 5'-CCCTTTGCTTCTATCTTGA-3') interfered with the RNA of...

Embodiment 3

[0074] Example 3 The mechanism of DDX19A promoting the metastasis of cervical squamous cell carcinoma cells

[0075] (1) DDX19A regulates NOX1 expression and increases ROS production in cervical squamous cell carcinoma.

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Abstract

The invention belongs to the technical field of medical products, and discloses an application to promotion of squamous cell carcinoma metastasis based on DDX19A. In function, DDX19A is found to promote in-vitro migration and invasion of cervical squamous cell carcinoma cells and in-vivo lung metastasis. In terms of mechanism, overexpression of the DDX19A increases NOX1 expression, increases production of reactive oxygen species (ROS), and induces migration and invasion of the cervical squamous cell carcinoma cells. Rescue experiments show that overexpression of NOX1 can retrieve and knock down cervical cancer squamous cell carcinoma cell invasion and migration and ROS generation caused by DDX19A, and the inventor further discovers that an ROS inhibitor N-acetylcysteine can inhibit DDX19A-induced cervical squamous cell carcinoma cell invasion and migration. Therefore, the DDX19A is proved to promote metastasis of the cervical squamous cell carcinoma by inducing NOX1 to mediate ROS production. Blocking of a DDX19A / NOX1 / ROS axis can be a potential therapeutic target for patients with cervical squamous cell carcinoma.

Description

technical field [0001] The present invention relates to the technical field of medical products, more specifically, to the application of DDX19A in promoting metastasis of cervical squamous cell carcinoma. Background technique [0002] Cervical cancer is one of the most common gynecological malignancies and the second leading cause of cancer-related death in women worldwide. Despite advances in surgery, chemotherapy, radiation therapy, and immunotherapy, the 5-year survival rate for cervical cancer patients has increased to 80%. However, once local or distant metastasis occurs, the 5-year survival rate decreases to about 50%. Metastasis is the main cause of death in cervical cancer patients. Cervical squamous cell carcinoma is the most common pathological type, accounting for approximately 80% of all cases. Therefore, it is extremely important to elucidate the underlying mechanism of cervical squamous cell carcinoma metastasis and identify new targets. [0003] Character...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886A61K45/00A61P35/00
CPCA61K45/00A61P35/00C12Q1/6886C12Q2600/118C12Q2600/158
Inventor 何欢欢陈勇刘继红蒋艳辉王柏彬黎永良
Owner THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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