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CN-122005869-A - Application of GABRD gene expression inhibitor in preparation of medicines for inhibiting liver cancer cell lung metastasis

CN122005869ACN 122005869 ACN122005869 ACN 122005869ACN-122005869-A

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of GABRD gene expression inhibitor in preparation of medicines for inhibiting liver cancer cell lung metastasis. GABRD gene expression inhibitor is a CRISPR-Cas9 tool for targeted knockout or knockout of GABRD gene and related biological reagents, wherein the sense strand sequence of sgRNA of the CRISPR-Cas9 tool is shown as SEQ ID NO. 1. Experiments prove that inhibiting GABRD gene expression can obviously inhibit liver cancer cell lung metastasis.

Inventors

  • ZHENG LU
  • You nan
  • WANG CHAOQUN
  • HUANG CHENGCHENG
  • LIU WEIWEI

Assignees

  • 中国人民解放军陆军军医大学第二附属医院

Dates

Publication Date
20260512
Application Date
20260326

Claims (10)

  1. Application of GABRD gene expression inhibitor in preparation of medicines for inhibiting lung metastasis of hepatoma cells, GABRD gene expression inhibitor is CRISPR-Cas9 tool for targeted knockout or knockdown of GABRD gene, wherein the sense strand sequence of sgRNA of CRISPR-Cas9 tool is shown as SEQ ID NO. 1.
  2. Application of GABRD gene expression inhibitor in preparing medicine for inhibiting liver cancer cell lung metastasis, GABRD gene expression inhibitor is recombinant expression vector for targeted inhibition of GABRD gene expression, the recombinant expression vector comprises CRISPR-Cas9 tool, and sense strand sequence of sgRNA of RISPR-Cas9 tool is shown as SEQ ID NO. 1.
  3. 3. Use according to claim 2, characterized in that the recombinant expression vector is obtained by embedding sgRNA into a LENTICRISPRV plasmid vector.
  4. The application of the GABRD gene expression inhibitor in preparing medicines for inhibiting lung metastasis of liver cancer cells is characterized in that the GABRD gene expression inhibitor is recombinant engineering bacteria for targeted inhibition of GABRD gene expression, the recombinant engineering bacteria are obtained by transduction of recombinant expression vectors into engineering bacteria, the recombinant expression vectors comprise CRISPR-Cas9 tools, and sense strand sequences of sgRNAs of RISPR-Cas9 tools are shown as SEQ ID NO. 1.
  5. 5. The use according to claim 4, wherein the engineering bacteria is E.coli.
  6. 6. The use according to any one of claims 1 to 5, wherein the medicament is in the form of an injection or powder.
  7. 7. The drug for inhibiting lung metastasis of liver cancer cells is characterized by comprising a CRISPR-Cas9 tool for targeted knockout or knocking down of GABRD genes and related biological reagents, wherein the sense strand sequence of sgRNA of the CRISPR-Cas9 tool is shown as SEQ ID NO. 1; Wherein the related biological reagent is a recombinant expression vector or recombinant engineering bacteria; The recombinant expression vector comprises a CRISPR-Cas9 tool; the recombinant engineering bacteria are obtained by transduction of recombinant expression vectors into engineering bacteria.
  8. 8. The drug according to claim 7, characterized in that the recombinant expression vector is obtained by embedding sgRNA into LENTICRISPRV plasmid vector.
  9. 9. The drug according to claim 7, wherein the engineering bacteria is escherichia coli.
  10. 10. A medicament according to any of claims 7 to 9, in the form of an injection or powder.

Description

Application of GABRD gene expression inhibitor in preparation of medicines for inhibiting liver cancer cell lung metastasis Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of GABRD gene expression inhibitor in preparation of medicines for inhibiting liver cancer cell lung metastasis. Background Liver cancer is one of the most prevalent malignant tumors in both morbidity and mortality worldwide, with the hepatocellular carcinoma being the highest. Because of the hidden early symptoms of liver cancer, most patients are in middle and late stages when diagnosed, and the patients are seriously threatened by tumor invasion and distant metastasis. Lung is the most common distant metastasis target organ for liver cancer, and liver cancer cell lung metastasis is one of the main causes of treatment failure and poor prognosis of patients. Clinical data show that after lung metastasis occurs in liver cancer patients, the survival rate is obviously reduced for 5 years, so that development of treatment strategies and medicaments capable of effectively inhibiting liver cancer cell lung metastasis has important clinical significance and social value for improving prognosis of liver cancer patients and survival rate. At present, the treatment means aiming at liver cancer metastasis mainly comprise surgical excision metastasis, radiotherapy, chemotherapy, targeted therapy, immunotherapy and the like. However, the surgical excision is only suitable for a few patients with limited metastasis, most patients with advanced metastasis cannot tolerate the surgical excision, the problems of poor targeting property, strong side effect and the like of radiotherapy and chemotherapy are solved, normal tissues are easy to damage, and tumor cells are easy to generate drug resistance after long-term use, and the existing targeting drugs and immunotherapy drugs show curative effects in part of patients, but still have the defects of limited applicable population, large individual difference of treatment effects and the like, and are difficult to meet the clinical requirements of liver cancer metastasis treatment. Therefore, the molecular mechanism of liver cancer cell lung metastasis is deeply explored, key regulatory genes are mined, and targeted intervention means are developed, so that the method becomes an important direction in the current liver cancer research field. GABRD gene codes gamma-aminobutyric acid A type receptor delta subunit, the receptor belongs to ligand-gated ion channel family, and the receptor is mainly involved in the inhibitory nerve conduction regulation of central nervous system. In recent years, with the deep research of tumor molecular biology, partial neurotransmitter receptor related genes are found to play an abnormal regulation role in the tumorigenesis and development process, but the relevance of GABRD genes and liver cancer cell metastasis has not been clearly reported. In the prior art, related researches on GABRD gene expression inhibition to regulate liver cancer cell lung metastasis are not carried out, and anti-liver cancer lung metastasis drugs based on GABRD gene expression inhibition are not developed. Based on the above, the effect of GABRD genes in liver cancer cell lung metastasis is excavated, the expression inhibitor of the targeted GABRD genes is developed and applied to preparation of medicaments for resisting liver cancer lung metastasis, and the method has important research value and clinical application prospect. Disclosure of Invention Based on the above, the invention aims to provide an application of GABRD gene expression inhibitor in preparing medicines for inhibiting liver cancer cell lung metastasis. In order to achieve the above purpose, the present invention may adopt the following technical scheme: The invention provides an application of GABRD gene expression inhibitor in preparing medicines for inhibiting liver cancer cell lung metastasis, wherein the GABRD gene expression inhibitor is a CRISPR-Cas9 tool for targeted knockout or knockdown of GABRD genes, and the sense strand sequence of sgRNA of the CRISPR-Cas9 tool is shown as SEQ ID NO. 1. Preferably, in the above application, the dosage form of the medicament is injection or powder. The invention also provides an application of GABRD gene expression inhibitor in preparing medicines for inhibiting liver cancer cell lung metastasis, wherein the GABRD gene expression inhibitor is a recombinant expression vector for targeted inhibition of GABRD gene expression, the recombinant expression vector comprises a CRISPR-Cas9 tool, and the sense strand sequence of sgRNA of the RISPR-Cas9 tool is shown as SEQ ID NO. 1. Preferably, in the above application, the recombinant expression vector is obtained by embedding sgRNA into LENTICRISPRV plasmid vector. Preferably, in the above application, the dosage form of the medicament is injection or powder. In still an