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CN-121971591-A - Application of FGF4 as drug target in treatment of enameloblastoma

CN121971591ACN 121971591 ACN121971591 ACN 121971591ACN-121971591-A

Abstract

The invention provides application of FGF4 as a drug target in treatment of enameloblastoma, relates to the technical field of biological medicine, and for the first time discovers potential effect of FGF4 in the enameloblastoma, proves that the FGF4 can be used as a treatment target of the enameloblastoma, experiments prove that the FGF4 gene can be knocked down in the enameloblastoma cell line to inhibit cell proliferation, cell migration, cell invasion and cell colony formation, and the FGF4 gene can be knockdown in an animal body to inhibit the growth of the enameloblastoma, so that the FGF4 has the effect of regulating the growth of the enameloblastoma, and the FGF4 inhibitor can inhibit the proliferation, migration, invasion and cell colony formation of the enameloblastoma cell line to inhibit the growth of the enameloblastoma. Provides a new therapeutic target for preventing and/or treating the enameloblastoma and has wide clinical application value.

Inventors

  • ZHANG RAN
  • HAN MENGJIE
  • XU TIANYI
  • LIANG JINCHU
  • CAO SHU

Assignees

  • 北京大学口腔医学院

Dates

Publication Date
20260505
Application Date
20260203

Claims (10)

  1. 1. Application of any one of A1 to A3 in preparing a product for preventing and/or treating enameloblastoma; A1, FGF4 gene; a2, FGF4 protein; a3, FGF4 inhibitor.
  2. 2. The use of claim 1, wherein the treatment of an ameloblast comprises inhibition of ameloblast growth.
  3. 3. The use of claim 2, wherein inhibiting the growth of the enameloblastoma comprises inhibiting proliferation of the enameloblastoma cell line, inhibiting migration of the enameloblastoma cell line, inhibiting invasion of the enameloblastoma cell line, and inhibiting colony formation of the enameloblastoma cell line.
  4. 4. The use according to any one of claims 1 to 3, wherein the FGF4 inhibitor comprises a substance that inhibits the expression, silencing or knocking out the FGF4 gene of FGF4 and/or a substance that reduces the content and/or activity of FGF4 protein.
  5. 5. The use of claim 4, wherein the substance comprises at least one of a nucleic acid molecule, a carbohydrate, a lipid, a small molecule compound, an antibody, a polypeptide, a protein, a gene editing vector, a lentivirus, or an adeno-associated virus.
  6. 6. The use of claim 5, wherein the nucleic acid molecule comprises an shRNA comprising any of B1-B3: b1, the shRNA targets and interferes with FGF4 genes; B2, the target sequence of the shRNA is shown as SEQ ID NO. 1; b3, the sense strand and the antisense strand of the interfering sequence of the shRNA are respectively shown as SEQ ID NO.2 and SEQ ID NO. 3.
  7. 7. The use according to claim 1, wherein the product comprises an FGF4 inhibitor; The product comprises an agent and/or a drug.
  8. 8. A medicament comprising the FGF4 inhibitor of any one of claims 1-7, for use in at least one of inhibiting enameloblastoma growth, inhibiting enameloblastoma cell line proliferation, inhibiting enameloblastoma cell line migration, inhibiting enameloblastoma cell line invasion, or inhibiting enameloblastoma cell line colony formation.
  9. 9. Application of any one of A1-A3 in screening candidate drugs for preventing and/or treating ameloblast: A1, FGF4 gene; a2, FGF4 protein; a3, FGF4 inhibitor.
  10. 10. The use according to claim 9, wherein the screening method comprises screening the drug or agent to be screened for FGF4 as target, to reduce the level of FGF4 gene expression or to reduce the amount or activity of FGF4 protein, as candidate drug for the prevention and/or treatment of enameloblastoma.

Description

Application of FGF4 as drug target in treatment of enameloblastoma Technical Field The invention relates to the technical field of biological medicine, in particular to application of FGF4 serving as a drug target in treatment of ameloblast. Background The enameloblastoma is an oral and maxillofacial benign tumor with strong invasiveness and extremely high recurrence rate, is formed by abnormal proliferation of dental plate Serres epithelium which is not completely degenerated during embryo development, and is a currently recognized pathological cause of mutation of BRAF600V gene. FGF4, fibroblast growth factor 4, is a protein that plays a critical role in embryonic development, cell proliferation and differentiation, and functions in FGF signaling through binding to FGFR (receptor). Its main receptors are FGFR1, FGFR2, FGFR3, FGFR4, and after binding to the receptor, FGF4 activates various downstream signaling pathways such as MARK, thereby acting. In the research of FGF4, cancer has been studied on lung cancer, esophageal squamous cell carcinoma, breast cancer and hepatocellular carcinoma, and more research is focused on the directions of embryo development, regenerative medicine, diabetes and the like, and in the research of livers, FGF4 is considered to protect the livers from nonalcoholic fatty liver by activating an AMP-activated protein kinase-Caspase 6 signal axis. Among the enameloblastomas, little research has been done on FGF, focusing mainly on FGF1 and FGF2, and the role of FGF4 in enameloblastomas is not known. Lentiviruses have been widely used in the field of tumor therapy as an effective gene vector. Specific therapeutic genes (such as tumor suppressor genes, immune regulatory factors and the like) can be transferred into tumor cells or immune system cells through lentiviral vectors, so that the targeted treatment of tumors or the delay of tumor progression is realized. There are still a number of limitations in practical applications. First, the targeting of the treatment is poor, and the existing lentiviral treatment methods cannot be fully directed against tumor cells, which may cause the normal cells to be affected, thereby increasing the side effects of the treatment. Second, the therapeutic effect is often unstable, the effect of lentiviral vectors in different tumor types varies significantly, and the efficacy may be compromised due to the heterogeneity of tumor cells and their resistance. Thirdly, lentiviruses as exogenous gene vectors may trigger rejection of the immune system, thereby affecting the therapeutic effect and triggering additional side effects. Finally, integration of lentiviral genes in host cells can present potential safety hazards, such as risk of genetic mutation or cancer, particularly over long periods or multiple uses. In view of this, the present invention has been made. Disclosure of Invention The invention aims to provide application of FGF4 gene, FGF4 protein or FGF4 inhibitor in preparation of products for preventing and/or treating enameloblastoma, so as to solve the technical problem that an action target for treating the enameloblastoma is lacking in the prior art. The second object of the present invention is to provide a medicament. The invention also aims to provide application of the FGF4 gene, the FGF4 protein or the FGF4 inhibitor in screening candidate medicines for preventing and/or treating the enameloblastoma. In order to achieve the above object of the present invention, the following technical solutions are specifically adopted: In a first aspect, the present invention provides the use of an FGF4 gene, an FGF4 protein, or an FGF4 inhibitor for the preparation of a product for the prevention and/or treatment of ameloblastic tumors. Further, the treatment of the enameloblastoma includes inhibiting enameloblastoma growth. Further, the inhibition of the growth of the enameloblastoma comprises inhibition of proliferation of enameloblastoma cell lines, inhibition of migration of enameloblastoma cell lines, inhibition of invasion of enameloblastoma cell lines and inhibition of colony formation of enameloblastoma cell lines. Further, the FGF4 inhibitor includes a substance that inhibits FGF4 gene expression, silences or knocks out the FGF4 gene, and/or a substance that reduces the content and/or activity of FGF4 protein. Further, the substance includes at least one of a nucleic acid molecule, a carbohydrate, a lipid, a small molecule compound, an antibody, a polypeptide, a protein, a gene editing vector, a lentivirus, or an adeno-associated virus. Further, the nucleic acid molecule comprises shRNA, and the shRNA comprises any one of B1-B3: b1, the shRNA targets and interferes with FGF4 genes; B2, the target sequence of the shRNA is shown as SEQ ID NO. 1; b3, the sense strand and the antisense strand of the interfering sequence of the shRNA are respectively shown as SEQ ID NO.2 and SEQ ID NO. 3. Further, the product comprises an FGF4 inhibitor and th