CN-122005798-A - Application of IFI27 gene as liver cancer treatment target

Abstract

The invention relates to the technical field of biological medicines, in particular to application of an IFI27 gene as a liver cancer treatment target. The invention discovers that the IFI27 is obviously up-regulated in liver cancer tissues for the first time, and has lower expression level in normal tissues beside cancer, and shows good tumor specificity, thus indicating that the IFI27 plays an important role in liver cancer progression. Furthermore, in vitro cell experiments prove that the proliferation activity, the clonogenic capacity and the migration invasive capacity of a liver cancer cell line can be obviously inhibited by utilizing the shRNA to knock down the IFI27 expression, and powerful evidence is provided for the IFI27 gene as a liver cancer treatment target. It was further verified in animals that knocking down IFI27 expression can effectively inhibit liver tumor growth. In conclusion, the IFI27 can be used as a potential new target point of liver cancer targeted therapy, and the small molecule inhibitor or biological agent aiming at the IFI27 has research value and clinical transformation potential for developing innovative medicaments for liver cancer. The invention provides a new theoretical basis and an intervention strategy for the accurate treatment of liver cancer.

Inventors

• REN ZHIGANG
• Ge Feilin
• YU ZUJIANG
• YU JIA

Assignees

• 郑州大学第一附属医院

Dates

Publication Date

20260512

Application Date

20251230

Claims (6)

1. 1. The application of a substance for inhibiting the activity of IFI27 protein or reducing the expression of a coding gene thereof in preparing medicines for treating liver cancer is provided.
2. 2. The use according to claim 1, wherein the active ingredient of the medicament is any one of a gene editing reagent for specifically knocking out the IFI27 encoding gene, or a small interfering RNA for specifically inhibiting the activity of the IFI27 protein or reducing the expression of the encoding gene thereof, or a small compound for specifically inhibiting the activity of the IFI27 protein or reducing the expression of the encoding gene thereof, or an antibody or ligand specifically binding to the IFI27 protein.
3. 3. The use according to claim 2, wherein the active ingredient of the medicament is shRNA, siRNA, dsRNA, miRNA, sgRNA which is an artificially designed functional RNA which specifically inhibits the activity of the IFI27 protein or reduces the expression of the gene encoding it.
4. 4. The use according to claim 3, wherein the active ingredient of the medicament is an artificially designed functional RNA which specifically inhibits the activity of the IFI27 protein or reduces the expression of the encoding gene thereof, is a shRNA which knocks out the IFI27 gene or a vector for expressing the shRNA, and the vector is any one of a plasmid vector, a lentiviral vector or an adeno-associated viral vector.
5. 5. The use according to claim 4, wherein the nucleotide sequence of the shRNA knocked down IFI27 gene is SEQ ID NO. 1, in particular shRNA-1:5'-GGATCCGAGTTCATCCTGGGCTCCATTGCTCGAGCAATGGAGCCCAGGATGAACTTTTTTTGAATTC-3'.
6. Application of IFI27 protein and its coding gene as biomarker in preparing liver cancer diagnosis kit.

Description

Application of IFI27 gene as liver cancer treatment target Technical Field The invention relates to the technical field of biological medicines, in particular to application of an IFI27 gene as a liver cancer treatment target. Background Liver malignancy, particularly hepatocellular carcinoma (HCC), is one of the most common malignant tumors worldwide, with both morbidity and mortality remaining high. The pathogenesis of liver cancer is complex, and involves abnormal regulation of various genes and signal pathways. At present, the treatment means of liver cancer mainly comprise surgical excision, liver transplantation, radio frequency ablation, chemotherapy, targeted treatment and the like, but most patients are in middle and late stages when diagnosis is confirmed due to the characteristics of high invasiveness, easy recurrence and metastasis of the liver cancer, so that the treatment effect is poor and the prognosis is poor. Therefore, finding new therapeutic targets and developing more effective therapeutic agents are of great clinical significance. Interferon-inducible protein 27 (Interferon alpha-inducible protein, IFI 27) is an interferon-stimulated gene (ISG) that is expressed by interferon during viral infection and immune response. The IFI27 protein is positioned on the mitochondrial membrane, the endoplasmic reticulum membrane and the nuclear membrane and participates in the biological processes of regulating apoptosis, immune response, virus replication and the like. In recent years, IFI27 has been found to be abnormally expressed in a variety of malignant tumors and is closely related to the occurrence, development, invasion and metastasis of the tumors. However, the specific role of IFI27 in liver malignancy and its potential as a therapeutic target has not been fully studied and demonstrated. The current targeted therapies for liver cancer have focused mainly on (1) anti-angiogenic drugs such as sorafenib (Sorafenib) and lenvatinib (Lenvatinib) blocking tumor angiogenesis by inhibiting Vascular Endothelial Growth Factor Receptor (VEGFR) and other kinase activities. These drugs are the first-line therapeutic drugs for advanced liver cancer at present, but can only prolong the survival time of patients for months, and have the problem of drug resistance. (2) Immune checkpoint inhibitors such as PD-1/PD-L1 inhibitors (Na Wu Liyou mab, pabo Li Zhushan antibody, etc.) and CTLA-4 inhibitors attack tumor cells by activating the immune system of the body. The medicine shows a certain curative effect in part of liver cancer patients, but the overall effective rate is still low, and immune related adverse reactions exist. (3) Targeted drugs against specific signaling pathways, such as mTOR inhibitors, c-Met inhibitors, etc., which interfere with critical signaling pathways in the development and progression of liver cancer. However, clinical studies have shown that the single drug efficacy of these drugs is limited and often accompanied by the development of drug resistance. (4) Gene therapy and RNA interference techniques, by regulating the expression of specific genes to inhibit tumor growth, such as gene silencing or over-expression strategies for certain oncogenes or tumor suppressor genes. However, these techniques are still in the research stage and have not been widely used in clinic. However, the existing liver cancer treatment technical scheme has a plurality of defects and limited curative effects (1) the overall effective rate of the existing targeted drugs and immunotherapeutic drugs is low, and most patients can only obtain a lifetime extension of a plurality of months and cannot realize long-term survival or cure. (2) The drug resistance problem is that whether the drug is a chemotherapeutic drug or a targeting drug, liver cancer cells are easy to generate drug resistance, so that the treatment fails. The drug resistance mechanism is complex, and the compensatory activation and gene mutation of various signal paths are involved. (3) The existing therapeutic drugs often have serious adverse reactions, such as liver and kidney function damage, bone marrow suppression, immune related adverse reactions and the like, seriously affect the life quality of patients, and part of patients are forced to terminate the treatment due to intolerance. (4) The lack of specific targets is that the pathogenesis of liver cancer is complex, the abnormality of a plurality of genes and signal paths is involved, and the lack of targeting to specific markers of liver cancer in the existing medicines leads to insufficient treatment selectivity and accuracy. Disclosure of Invention The invention aims to provide a new therapeutic target for treating liver cancer. In order to achieve the above purpose, the invention provides the application of the substance for inhibiting the activity of the IFI27 protein or reducing the expression of the coding gene thereof in preparing the medicines for treating liver cancer. Specif